Ferroptosis-centered Disease Response Information
General Information of the Disease (ID: DIS00026)
Name |
Gastric cancer
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ICD |
ICD-11: 2B72
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Full List of Target(s) of This Ferroptosis-centered Disease
Polyunsaturated fatty acid lipoxygenase ALOX15 (ALOX15)
In total 3 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [1] | ||||
Target for Ferroptosis | Driver | ||||
Responsed Disease | Gastric cancer [ICD-11: 2B72] | ||||
Responsed Drug | Cisplatin | Investigative | |||
Responsed Regulator | hsa-mir-522 (Precursor RNA) | Suppressor | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
In Vitro Model | SGC-7901 cells | Gastric carcinoma | Homo sapiens | CVCL_0520 | |
MGC-803 cells | Gastric mucinous adenocarcinoma | Homo sapiens | CVCL_5334 | ||
MKN45 cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0434 | ||
In Vivo Model |
Male nude mice (BALB/c-nu, 6B8 weeks) were housed in a pathogen free animal facility with access to water and food, and allowed to eat and drink adlibitum. 5 x 105 SGC7901 cells and CAFs were injected subcutaneously for one mouse. These tumor-implanted mice were injected with either cisplatin (5 ug/g) or saline every 5 days since the day ten, and were sacrificed and tumors were removed at the 30th Day.
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Response regulation | Cisplatin and paclitaxel promote miR-522 secretion from CAFs by activating USP7/hnRNPA1 axis, leading to ALOX15 suppression and decreased lipid-ROS accumulation in cancer cells, and ultimately result in decreased chemo-sensitivity. The intercellular pathway, comprising USP7, hnRNPA1, exo-miR-522 and ALOX15, reveals new mechanism of acquired chemo-resistance in gastric cancer. | ||||
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target | [1] | ||||
Target for Ferroptosis | Driver | ||||
Responsed Disease | Gastric cancer [ICD-11: 2B72] | ||||
Responsed Drug | Paclitaxel | Investigative | |||
Responsed Regulator | hsa-mir-522 (Precursor RNA) | Suppressor | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
In Vitro Model | SGC-7901 cells | Gastric carcinoma | Homo sapiens | CVCL_0520 | |
MGC-803 cells | Gastric mucinous adenocarcinoma | Homo sapiens | CVCL_5334 | ||
MKN45 cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0434 | ||
In Vivo Model |
Male nude mice (BALB/c-nu, 6B8 weeks) were housed in a pathogen free animal facility with access to water and food, and allowed to eat and drink adlibitum. 5 x 105 SGC7901 cells and CAFs were injected subcutaneously for one mouse. These tumor-implanted mice were injected with either cisplatin (5 ug/g) or saline every 5 days since the day ten, and were sacrificed and tumors were removed at the 30th Day.
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Response regulation | Cisplatin and paclitaxel promote miR-522 secretion from CAFs by activating USP7/hnRNPA1 axis, leading to ALOX15 suppression and decreased lipid-ROS accumulation in cancer cells, and ultimately result in decreased chemo-sensitivity. The intercellular pathway, comprising USP7, hnRNPA1, exo-miR-522 and ALOX15, reveals new mechanism of acquired chemo-resistance in gastric cancer. | ||||
Experiment 3 Reporting the Ferroptosis-centered Disease Response by This Target | [10] | ||||
Target for Ferroptosis | Driver | ||||
Responsed Disease | Gastric cancer [ICD-11: 2B72] | ||||
Responsed Regulator | Perilipin-2 (PLIN2) | Suppressor | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Apoptosis | hsa04210 | ||||
Cell Process | Cell ferroptosis | ||||
Cell apoptosis | |||||
Cell proliferation | |||||
In Vitro Model | SGC-7901 cells | Gastric carcinoma | Homo sapiens | CVCL_0520 | |
MGC-803 cells | Gastric mucinous adenocarcinoma | Homo sapiens | CVCL_5334 | ||
In Vivo Model |
SGC7901 cell line transfected with OvPLIN2, ShPLIN2 and Control were injected subcutaneously into the nude mice (BALB/c nu/nu, female, 5 weeks old, Beijing Huafukang Biotechnology Co. Ltd. China) which were anaesthetized with 1% Sodium pentobarbital. The long diameter a and short diameter b of mouse tumor and the weights were measured every 4-5 days, and the relative tumor volumes (RTV) were calculated according to formula 0.5 x a x b x b.
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Response regulation | Overexpression and knockdown of PLIN2 augmented the proliferation and apoptosis of gastric carcinoma cell lines SGC7901 and MGC803, respectively. PLIN2 modulated Ferroptosis pathway through regulating transcription factors-PRDM11 and IPO7:ACSL3 was a critical gene involved in abnormal lipid metabolism, ALOX15 facilitated apoptosis and necrosis. | ||||
Phospholipid hydroperoxide glutathione peroxidase (GPX4)
In total 10 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [2] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Gastric cancer [ICD-11: 2B72] | ||||
Responsed Drug | Apatinib | Investigative | |||
Responsed Regulator | Sterol regulatory element-binding protein 1 (SREBF1) | Suppressor | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Glutathione metabolism | hsa00480 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | MGC-803 cells | Gastric mucinous adenocarcinoma | Homo sapiens | CVCL_5334 | |
MKN45 cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0434 | ||
BGC-823 cells | Gastric carcinoma | Homo sapiens | CVCL_3360 | ||
SGC-7901 cells | Gastric carcinoma | Homo sapiens | CVCL_0520 | ||
AGS cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0139 | ||
In Vivo Model |
Female nude mice (BALB/c, nu/nu, 18-22 g, 4-5 weeks old) were obtained from Guangdong Medical Laboratory Animal center, China, and maintained under specific pathogen-free conditions on a 12h/12h light/dark cycle. Each mouse was injected subcutaneously with eight million luciferase-expressing cells resuspended in 50 ul of PBS and 50 ul of Matrigel (BD Biosciences). When a palpable mass had developed, the mice were randomly divided into five groups: apatinib (50 mg/kg/day oral dose for 14 days); RSL3 (100 mg/kg injection of RSL3 twice per week for 2 weeks at the same site); both; apatinib (50 mg/kg/day oral dose for 14 days) plus vitamin E (100 mg/kg/day oral dose for 14 days); and vehicle (DMSO, 100 ul oral dose for 14 days).
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Response regulation | Apatinib exerted antitumor effects against gastric cancer cells in vitro and in vivo through the induction of lipid peroxidation mediated by GPX4, then lead to ferroptosis. Furethermore, we found apatinib inhibited transcription of GPX4 via a SREBP1a-mediated pathway. These results indicated that GPX4 may be a potential target for anti-GC efficacy evaluation and treatment of apatinib. | ||||
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target | [11] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Gastric cancer [ICD-11: 2B72] | ||||
Responsed Drug | (6R,6aR,9S,11bS,14R)-4,4-Dimethyl-8-methylene-7,11,12-trioxododecahydro-1H-6,11b-(epoxymethano)-6a,9-methanocyclohepta[a]naphthalen-14-yl valinate | Investigative | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Autophagy | hsa04140 | ||||
Apoptosis | hsa04210 | ||||
Cell Process | Cell ferroptosis | ||||
Cell apoptosis | |||||
Cell autophagy | |||||
Cell proliferation | |||||
In Vitro Model | HGC-27 cells | Gastric carcinoma | Homo sapiens | CVCL_1279 | |
MGC-803 cells | Gastric mucinous adenocarcinoma | Homo sapiens | CVCL_5334 | ||
BGC-823 cells | Gastric carcinoma | Homo sapiens | CVCL_3360 | ||
AGS cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0139 | ||
GES-1 cells | Normal | Homo sapiens | CVCL_EQ22 | ||
In Vivo Model |
Male nude mice (ages 6-8 weeks) used in the studies were purchased from Hunan SJA Laboratory Animal Co. (Changsha, China). Male nude mice were subcutaneously injected with MGC-803cells into the right flank of mouse. Once the tumor volume reached 100-200 mm3, mice were randomly divided into 5 groups (6 mice/group) and administered with saline,a2(5, 10, and 20 mg/kg), or 5-fluorouracil (5-FU, 15mg/kg) once a day for 21 daysviatail vein injection.
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Response regulation | (6R,6aR,9S,11bS,14R)-4,4-Dimethyl-8-methylene-7,11,12-trioxododecahydro-1H-6,11b-(epoxymethano)-6a,9-methanocyclohepta[a]naphthalen-14-yl valinate (a2), a new JDA derivative, inhibited the growth of gastric cancer cells. Importantly, compounda2decreased GPX4 expression and overexpressing GPX4 antagonized the anti-proliferative activity ofa2. Furthermore, a2caused ferrous iron accumulation through the autophagy pathway, prevention of which rescueda2induced ferrous iron elevation and cell growth inhibition. | ||||
Experiment 3 Reporting the Ferroptosis-centered Disease Response by This Target | [12] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Gastric cancer [ICD-11: 2B72] | ||||
Responsed Drug | Actinidia chinensis Planch | Investigative | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Apoptosis | hsa04210 | ||||
Cell Process | Cell ferroptosis | ||||
Cell apoptosis | |||||
Cell proliferation | |||||
Cell migration | |||||
In Vitro Model | HGC-27 cells | Gastric carcinoma | Homo sapiens | CVCL_1279 | |
In Vivo Model |
Wild type AB strain of zebrafish (Danio rerio) was obtained from Southern Medical University. The HGC-27 cells labeled with EGFP were resuspended in PBS in the concentration of 5*107/ml. 10 nl cell suspension containing approximately 300 cells were loaded into capillary needles and injected into the abdominal perivitelline space of zebrafish embryos by a nanoliter injector (Narishige, Tokyo, Japan). After injection, the tumor-bearing embryos were transferred into a 24-well plate and acclimated in embryo water at 35 for 24 h and then incubated at 0, 90, 180 mg/ml ACP decoction for 48 h.
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Response regulation | Actinidia chinensis Planch (ACP) increased the accumulation of ROS via inhibited the glutathione peroxidase 4 (GPx4) and xCT (SLC7A11) proteins, while were inhibited by Ferrostatin-1 (Fer-1) significantly. In conclusion, ACP was a promising antineoplastic agent for the treatment of gastric cancer by regulating apoptosis, ferroptosis and mesenchymal phenotype. | ||||
Experiment 4 Reporting the Ferroptosis-centered Disease Response by This Target | [13] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Gastric cancer [ICD-11: 2B72] | ||||
Responsed Drug | Atranorin | Investigative | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Fatty acid metabolism | hsa01212 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | hGCCs (Gastric cancer cells) | ||||
In Vivo Model |
NOD-scid mice (NOD.CB17-Prkdcscid/NcrCrl) aged 6-7 weeks and weighing 20-22 g were used in the experiment. The animal study was performed at the Shanghai University of Traditional Chinese Medicine with approval from the Institutional Animal Care and Use Committee in accordance with the institutional guidelines. All mice were randomly divided into two groups, and each group consisted of four mice. In experimental group, approximately 1 x 105 GCSCs in logarithmic growth phase were harvested and inoculated subcutaneously into NOD-scid mice, and intraperitoneal injection of 100 ul Atranorin@SPION (10 mg/kg) every 2 days. In control group, approximately 1 x 105 GCSCs in logarithmic growth phase were harvested and inoculated subcutaneously into NOD-scid mice, and intraperitoneal injection of 100 ul SPION (10 mg/kg) alone every 2 days. After 2 months, the mice were sacrificed, and their tumors were excised.
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Response regulation | Atranorin@SPIONs significantly reduced the 5-hydroxymethylcytidine modification level of GPX4 and SLC7A11 mRNA 3' untranslated region in gastric cancer cells. This study revealed the molecular biological mechanism by which Atranorin@SPION inhibit the in vitro and in vivo activity of GCSCs, that is, Atranorin@SPION reduced the expression of members of the Xc-/GPX4 axis and reduced their mRNA 5-hydroxymethylcytidine modification, finally induced ferroptosis of GCSCs. | ||||
Experiment 5 Reporting the Ferroptosis-centered Disease Response by This Target | [8] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Gastric cancer [ICD-11: 2B72] | ||||
Responsed Drug | Polyphyllin B | Investigative | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Cell Process | Cell ferroptosis | ||||
Cell apoptosis | |||||
Cell proliferation | |||||
In Vitro Model | NUGC-3 cells | Gastric carcinoma | Homo sapiens | CVCL_1612 | |
MKN-1 cells | Gastric carcinoma | Homo sapiens | CVCL_1415 | ||
MKN45 cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0434 | ||
HGC-27 cells | Gastric carcinoma | Homo sapiens | CVCL_1279 | ||
NUGC-4 cells | Gastric signet ring cell adenocarcinoma | Homo sapiens | CVCL_3082 | ||
In Vivo Model |
The nude mice were raised in our laboratory for a week before the experiment. Then, 5 x 106 MKN-1 cells were subcutaneously injected to establish the subcutaneous xenograft tumour model in nude mice. When the maximum diameter of the xenograft tumours grew steadily to 1 cm, they were dissected completely and cut into 1 mm3 tissue fragments. Then, the tissue fragment was inserted into the surface of the serosa on the greater curvature of the stomach. Different doses of PB (2.5 mg/kg or 5.0 mg/kg) were given by intraperitoneal injection once a day for 3 weeks. The control group was given the same volume of vehicle. The positive control group was given 5-Fu at the dose of 10 mg/kg. The body weight and tumour size of nude mice were recorded. Mice were administered fluorescein substrate (150 mg/kg) intraperitoneally for in vivo imaging twice a week on a Xenogen IVIS 200 imaging system (Caliper Life Sciences, USA). The tumour inhibition rate was analysed using LT Living Image 4.3 Software.
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Response regulation | We identified a novel GPx4 inhibitor, polyphyllin B (PB), which can induce ferroptosis by down-regulating GPx4 expression in gastric cancer (GC) cells. It has also been shown to inhibit cell proliferation, suppress invasion and migration, induce apoptosis, and block the cell cycle progression in GC cellsin vitro. Then, immunofluorescence and western blotting assay confirmed that PB can regulate the expression of LC3B, TFR1, NOCA4 and FTH1in vitro, which suggested that suggest that PB may increase the level of Fe2+by transporting Fe3+into the cell by TFR1 and promoting NCOA4-dependent iron autophagy. | ||||
Experiment 6 Reporting the Ferroptosis-centered Disease Response by This Target | [14] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Gastric cancer [ICD-11: 2B72] | ||||
Responsed Drug | Thioguanine | Investigative | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
In Vitro Model | MGC-803 cells | Gastric mucinous adenocarcinoma | Homo sapiens | CVCL_5334 | |
AGS cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0139 | ||
In Vivo Model |
Female BALB/c nude mice (6-7 weeks, 17-18 g) were purchased from Hunan Slack Scene of Laboratory Animal Co., Ltd. and used to establish the xenograft mouse model with 5 x 106 exponentially growing MGC-803 cells inoculated subcutaneously into the right forelimb for each mouse. Once the volume of tumors reached 100 mm3, the mice were divided into 3 groups: solvent control; 6-TG (10 mg/kg/day); 6-TG (10 mg/kg/day) + Fer-1(50 mg/kg/day).
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Response regulation | 6-Thioguanine was identified as a potential ferroptosis inducer in gastric cancer cells for the first time. It could inactivate system xc, block the generation of GSH, down-regulate the expression of GPX4, increase the level of Lipid ROS, and finally trigger the Fe-2+-mediated ferroptosis in MGC-803 and AGS cell lines. | ||||
Experiment 7 Reporting the Ferroptosis-centered Disease Response by This Target | [9] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Gastric cancer [ICD-11: 2B72] | ||||
Responsed Drug | XN4 | Investigative | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | SGC-7901 cells | Gastric carcinoma | Homo sapiens | CVCL_0520 | |
BGC-823 cells | Gastric carcinoma | Homo sapiens | CVCL_3360 | ||
GES-1 cells | Normal | Homo sapiens | CVCL_EQ22 | ||
Response regulation | The pro-ferroptotic role of XN4 in gastric cancer (GC) might enable it to become a promising drug for GC treatment in the future despite the need for extensive research. Moreover, GPX4 levels decreased, but NOX4 and ferroptosis-related protein PTGS2 levels increased in GC cells following XN4 treatment, which was nullified by NOX4 knockdown. | ||||
Experiment 8 Reporting the Ferroptosis-centered Disease Response by This Target | [15] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Gastric cancer [ICD-11: 2B72] | ||||
Responsed Regulator | Transcriptional activator Myb (MYB) | Driver | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
In Vitro Model | AGS cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0139 | |
BGC-823 cells | Gastric carcinoma | Homo sapiens | CVCL_3360 | ||
MKN45 cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0434 | ||
SGC-7901 cells | Gastric carcinoma | Homo sapiens | CVCL_0520 | ||
MGC-803 cells | Gastric mucinous adenocarcinoma | Homo sapiens | CVCL_5334 | ||
In Vivo Model |
1 x 106 BGC823 control or CDO1 short hairpin (sh)RNA treated cells in 150 ul PBS were injected subcutaneously right of the dorsal midline in athymic nude mice. Once the tumors reached 80 to 100 mm3 at day 10, mice were allocated randomly into groups of five and treated with erastin (30 mg/kg intraperitoneally, twice every other day).
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Response regulation | Silencing CDO1 inhibited erastin-induced ferroptosis in gastric cancer cells both in vitro and in vivo. Mechanistically, c-Myb (MYB) transcriptionally regulated CDO1, and inhibition of CDO1 expression upregulated GPX4 expression. | ||||
Experiment 9 Reporting the Ferroptosis-centered Disease Response by This Target | [15] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Gastric cancer [ICD-11: 2B72] | ||||
Responsed Regulator | Cysteine dioxygenase type 1 (CDO1) | Driver | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
In Vitro Model | AGS cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0139 | |
BGC-823 cells | Gastric carcinoma | Homo sapiens | CVCL_3360 | ||
MKN45 cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0434 | ||
SGC-7901 cells | Gastric carcinoma | Homo sapiens | CVCL_0520 | ||
MGC-803 cells | Gastric mucinous adenocarcinoma | Homo sapiens | CVCL_5334 | ||
In Vivo Model |
1 x 106 BGC823 control or CDO1 short hairpin (sh)RNA treated cells in 150 ul PBS were injected subcutaneously right of the dorsal midline in athymic nude mice. Once the tumors reached 80 to 100 mm3 at day 10, mice were allocated randomly into groups of five and treated with erastin (30 mg/kg intraperitoneally, twice every other day).
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Response regulation | Silencing CDO1 inhibited erastin-induced ferroptosis in gastric cancer cells both in vitro and in vivo. Mechanistically, c-Myb transcriptionally regulated CDO1, and inhibition of CDO1 expression upregulated GPX4 expression. | ||||
Experiment 10 Reporting the Ferroptosis-centered Disease Response by This Target | [16] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Gastric cancer [ICD-11: 2B72] | ||||
Responsed Regulator | NAD-dependent protein deacylase sirtuin-6 (SIRT6) | Suppressor | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Pathways in cancer | hsa05200 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | NCI-N87 cells | Gastric tubular adenocarcinoma | Homo sapiens | CVCL_1603 | |
HGC-27 cells | Gastric carcinoma | Homo sapiens | CVCL_1279 | ||
Response regulation | SIRT6 inhibition led to the inactivation of the Keap1/Nrf2 signalling pathway and downregulation of GPX4. The overexpression of GPX4 or activation of Keap1/Nrf2 reverses the effects of the downregulation of SIRT6 on sorafenib-induced ferroptosis. Thus, targeting the SIRT6/Keap1/Nrf2/GPX4 signalling pathway may be a potential strategy for overcoming sorafenib resistance in gastric cancer. | ||||
Cystine/glutamate transporter (SLC7A11)
In total 12 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [3] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Gastric cancer [ICD-11: 2B72] | ||||
Responsed Drug | Levobupivacaine | Approved | |||
Responsed Regulator | hsa-miR-489-3p (miRNA) | Driver | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
In Vitro Model | GES-1 cells | Normal | Homo sapiens | CVCL_EQ22 | |
HGC-27 cells | Gastric carcinoma | Homo sapiens | CVCL_1279 | ||
SGC-7901 cells | Gastric carcinoma | Homo sapiens | CVCL_0520 | ||
In Vivo Model |
Ten SCID nude mice aged 6-8 weeks were purchased from Vital River Laboratory Animal Technology Co., Ltd. (Beijing, China), and subcutaneously injected with SGC7901 cells (5 x 106 cells per mouse) in left back. One week after feeding, the mice were randomly divided into two groups, the control and treatment group. For the next 25 days, the mice in treatment group were injected with erastin (15 mg/kg intraperitoneally) or co-treated with 40 mol/kg body weight of levobupivacaine once a day. The body weight and tumor size were measured every 3 days.
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Response regulation | Levobupivacaine-upregulated miR-489-3p enhanced ferroptosis of gastric cancer cells by targeting SLC7A11. MiR-489-3p was involved in levobupivacaine-induced ferroptosis of gastric cancer cells. Levobupivacaine/miR-489-3p/SLC7A11 axis attenuates gastric cancer cell proliferationin vitro. | ||||
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target | [4] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Gastric cancer [ICD-11: 2B72] | ||||
Responsed Drug | Tanshinone IIA | Investigative | |||
Responsed Regulator | Cellular tumor antigen p53 (TP53) | Driver | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
In Vitro Model | BGC-823 cells | Gastric carcinoma | Homo sapiens | CVCL_3360 | |
NCI-N87 cells | Gastric tubular adenocarcinoma | Homo sapiens | CVCL_1603 | ||
In Vivo Model |
All mice were housed under a setting of 12-h light/dark cycle at 22 ± 1, 55% humidity and fed with water and food provided at regular time. During the entire maintenance period, all mice were permitted free cage activity without joint immobilization. The initial body weights of the mice were between 20 and 23 grams. After subcutaneous injection of 2 x 106 BGC-823 gastric cancer cells into the back of NOD-SCID mice, the mice were treated with or without Tan IIA (50 mg/kg) or Tan IIA in combination with Fer-1 (50 mg/kg). Tan IIA was diluted in DMSO:Methanol:Hydroxypropyl-b-cydodextrin (HP-b-CD) = 1:1:1. Fer-1 was also dissolved in DMSO:Methanol:HP-b-CD. Seven days after BGC-823 gastric cancer cells injection, intraperitoneal injection with Tan IIA was carried out every other day followed by killing at day 22 of tumor cell inoculation. All mice were killed by dislocation of the cervical vertebrae. Before killing, the tumor volume was measured every 3 days. All experiments were carried out using six mice each group in three independent experiments of a time-dependent manner with three time points.
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Response regulation | Tanshinone IIA increased lipid peroxidation and up-regulated Ptgs2 and Chac1 expression, two markers of ferroptosis. In addition, Tan IIA also up-regulated p53 expression and down-regulated xCT (SLC7A11) expression. Therefore, Tan IIA could suppress the proliferation of gastric cancer via inducing p53 upregulation-mediated ferroptosis. | ||||
Experiment 3 Reporting the Ferroptosis-centered Disease Response by This Target | [12] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Gastric cancer [ICD-11: 2B72] | ||||
Responsed Drug | Actinidia chinensis Planch | Investigative | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Apoptosis | hsa04210 | ||||
Cell Process | Cell ferroptosis | ||||
Cell apoptosis | |||||
Cell proliferation | |||||
Cell migration | |||||
In Vitro Model | HGC-27 cells | Gastric carcinoma | Homo sapiens | CVCL_1279 | |
In Vivo Model |
Wild type AB strain of zebrafish (Danio rerio) was obtained from Southern Medical University. The HGC-27 cells labeled with EGFP were resuspended in PBS in the concentration of 5*107/ml. 10 nl cell suspension containing approximately 300 cells were loaded into capillary needles and injected into the abdominal perivitelline space of zebrafish embryos by a nanoliter injector (Narishige, Tokyo, Japan). After injection, the tumor-bearing embryos were transferred into a 24-well plate and acclimated in embryo water at 35 for 24 h and then incubated at 0, 90, 180 mg/ml ACP decoction for 48 h.
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Response regulation | Actinidia chinensis Planch (ACP) increased the accumulation of ROS via inhibited the glutathione peroxidase 4 (GPx4) and xCT (SLC7A11) proteins, while were inhibited by Ferrostatin-1 (Fer-1) significantly. In conclusion, ACP was a promising antineoplastic agent for the treatment of gastric cancer by regulating apoptosis, ferroptosis and mesenchymal phenotype. | ||||
Experiment 4 Reporting the Ferroptosis-centered Disease Response by This Target | [13] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Gastric cancer [ICD-11: 2B72] | ||||
Responsed Drug | Atranorin | Investigative | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Fatty acid metabolism | hsa01212 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | hGCCs (Gastric cancer cells) | ||||
In Vivo Model |
NOD-scid mice (NOD.CB17-Prkdcscid/NcrCrl) aged 6-7 weeks and weighing 20-22 g were used in the experiment. The animal study was performed at the Shanghai University of Traditional Chinese Medicine with approval from the Institutional Animal Care and Use Committee in accordance with the institutional guidelines. All mice were randomly divided into two groups, and each group consisted of four mice. In experimental group, approximately 1 x 105 GCSCs in logarithmic growth phase were harvested and inoculated subcutaneously into NOD-scid mice, and intraperitoneal injection of 100 ul Atranorin@SPION (10 mg/kg) every 2 days. In control group, approximately 1 x 105 GCSCs in logarithmic growth phase were harvested and inoculated subcutaneously into NOD-scid mice, and intraperitoneal injection of 100 ul SPION (10 mg/kg) alone every 2 days. After 2 months, the mice were sacrificed, and their tumors were excised.
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Response regulation | Atranorin@SPIONs significantly reduced the 5-hydroxymethylcytidine modification level of GPX4 and SLC7A11 mRNA 3' untranslated region in gastric cancer cells. This study revealed the molecular biological mechanism by which Atranorin@SPION inhibit the in vitro and in vivo activity of GCSCs, that is, Atranorin@SPION reduced the expression of members of the Xc-/GPX4 axis and reduced their mRNA 5-hydroxymethylcytidine modification, finally induced ferroptosis of GCSCs. | ||||
Experiment 5 Reporting the Ferroptosis-centered Disease Response by This Target | [21] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Gastric cancer [ICD-11: 2B72] | ||||
Responsed Regulator | Cyclic AMP-dependent transcription factor ATF-2 (ATF2) | Suppressor | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
In Vitro Model | GES-1 cells | Normal | Homo sapiens | CVCL_EQ22 | |
SGC-7901 cells | Gastric carcinoma | Homo sapiens | CVCL_0520 | ||
HGC-27 cells | Gastric carcinoma | Homo sapiens | CVCL_1279 | ||
AGS cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0139 | ||
MGC-803 cells | Gastric mucinous adenocarcinoma | Homo sapiens | CVCL_5334 | ||
MKN45 cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0434 | ||
In Vivo Model |
Four-week-old female BALB/c nude mice were purchased from SLAC Laboratory Animal Co., Ltd. (Shanghai, China). For subsequent studies, the nude mice were randomly divided into four groups as follows: sh-Ctrl, sh-ATF2, sh-Ctrl + sorafenib and sh-ATF2 + sorafenib. Approximately 5 x 106 ATF2 knockdown or control MGC803 cells were subcutaneously injected into the axilla of nude mice. Beginning on Day 8, mice in the sorafenib treatment group received 10 mg/kg sorafenib by intraperitoneal injection every 2 days for 3 weeks.
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Response regulation | Using ChIP-Seq and RNA-Seq, HSPH1 as a target of ATF2 and further validated it by ChIPqPCR analysis. HSPH1 can interact with SLC7A11 (cystine/glutamate transporter) and increase its protein stability. Importantly, knockdown of HSPH1 partly reversed the effects caused by ATF2 overexpression on sorafenib-induced ferroptosis in gastric cancer cells. | ||||
Experiment 6 Reporting the Ferroptosis-centered Disease Response by This Target | [22] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Gastric cancer [ICD-11: 2B72] | ||||
Responsed Regulator | ELAV-like protein 1 (ELAVL1) | Suppressor | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
In Vitro Model | AGS cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0139 | |
MGC-803 cells | Gastric mucinous adenocarcinoma | Homo sapiens | CVCL_5334 | ||
In Vivo Model |
For animal models of gastric subserosal injection, we collected MGC-803 cell lines (5 x 10 cells) that were infected by lentivirus with or without PMAN-OE, and suspended in 40 ul serum-free medium (50% Matrigel). After that, nude mice (six mice per group) were anesthetized by intraperitoneal injection of 100 ul of pentobarbital (1%). After disinfection, the abdominal cavity was opened to expose the greater curvature of the stomach. The tumor suspension (40 ul) was implanted under the serosa of the greater curvature of the stomach of the nude mice through an insulin needle.
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Response regulation | HIF-1 could act as a protective factor against ferroptosis in gastric cancer (GC) cells. HIF-1 activates PMAN at the transcriptional level, which greatly improves the output of ELAVL1 in the cytoplasm. ELAVL1 directly combines with the AREs of SLC7A11 mRNA 3-UTR and improves the stability of SLC7A11mRNA, thereby increasing the expression of SLC7A11 and reducing the accumulation of ROS and iron in ferroptosis, ultimately promoting the proliferation and development of tumor cells. | ||||
Experiment 7 Reporting the Ferroptosis-centered Disease Response by This Target | [23] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Gastric cancer [ICD-11: 2B72] | ||||
Responsed Regulator | Growth/differentiation factor 15 (GDF15) | Suppressor | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | MGC-803 cells | Gastric mucinous adenocarcinoma | Homo sapiens | CVCL_5334 | |
Response regulation | GDF15 knockdown promotes erastin-induced ferroptosis in gastric cancer cell MGC803 by attenuating the expression of SLC7A11 and the function of system Xc-. | ||||
Experiment 8 Reporting the Ferroptosis-centered Disease Response by This Target | [21] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Gastric cancer [ICD-11: 2B72] | ||||
Responsed Regulator | Heat shock protein 105 kDa (HSPH1) | Suppressor | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
In Vitro Model | GES-1 cells | Normal | Homo sapiens | CVCL_EQ22 | |
SGC-7901 cells | Gastric carcinoma | Homo sapiens | CVCL_0520 | ||
HGC-27 cells | Gastric carcinoma | Homo sapiens | CVCL_1279 | ||
AGS cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0139 | ||
MGC-803 cells | Gastric mucinous adenocarcinoma | Homo sapiens | CVCL_5334 | ||
MKN45 cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0434 | ||
In Vivo Model |
Four-week-old female BALB/c nude mice were purchased from SLAC Laboratory Animal Co., Ltd. (Shanghai, China). For subsequent studies, the nude mice were randomly divided into four groups as follows: sh-Ctrl, sh-ATF2, sh-Ctrl + sorafenib and sh-ATF2 + sorafenib. Approximately 5 x 106 ATF2 knockdown or control MGC803 cells were subcutaneously injected into the axilla of nude mice. Beginning on Day 8, mice in the sorafenib treatment group received 10 mg/kg sorafenib by intraperitoneal injection every 2 days for 3 weeks.
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Response regulation | Using ChIP-Seq and RNA-Seq, HSPH1 as a target of ATF2 and further validated it by ChIPqPCR analysis. HSPH1 can interact with SLC7A11 (cystine/glutamate transporter) and increase its protein stability. Importantly, knockdown of HSPH1 partly reversed the effects caused by ATF2 overexpression on sorafenib-induced ferroptosis in gastric cancer cells. | ||||
Experiment 9 Reporting the Ferroptosis-centered Disease Response by This Target | [24] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Gastric cancer [ICD-11: 2B72] | ||||
Responsed Regulator | hsa-miR-375-3p (miRNA) | Driver | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
Cell stemness | |||||
In Vitro Model | SGC-7901 cells | Gastric carcinoma | Homo sapiens | CVCL_0520 | |
BGC-823 cells | Gastric carcinoma | Homo sapiens | CVCL_3360 | ||
GES-1 cells | Normal | Homo sapiens | CVCL_EQ22 | ||
In Vivo Model |
Four- to eight-week-old female BALB/c nude mice were purchased from the Model Animal Research Center of Nanjing University (Nanjing, China). For the tumor-limiting dilution assay, 1 x 107, 5 x 106, and 2.5 x 106 of LV3-miR-375 cells, LV3-SLC7A11 cells, LV3-shSLC7A11 cells, LV3-miR-375-SLC7A11 cells, and LV3-NC cells (BGC-823 and SGC-7901) were subcutaneously implanted into the underarm of mice. Fifteen days later, all mice were euthanized and tumor tissues were collected and weighed. For metastasis experiment, mouse models were established by intravenous injection of cells. Three mice per group were injected with 2 x 106 cells in 200 uL RPMI-1640 serum-free media. Six weeks after injection, mice were sacrificed for collecting lung tissues.
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Response regulation | MiR-375 reduced the stemness of gastric cancer cells in vitro and in vivo. Mechanistically, SLC7A11 was identified as a direct target of miR-375 and miR-375 attenuated the stemness of GC cells mainly through triggering SLC7A11-dependent ferroptosis. | ||||
Experiment 10 Reporting the Ferroptosis-centered Disease Response by This Target | [25] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Gastric cancer [ICD-11: 2B72] | ||||
Responsed Regulator | hsa-miR-375-3p (miRNA) | Driver | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | MKN45 cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0434 | |
AGS cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0139 | ||
Hs746T cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0333 | ||
NCI-N87 cells | Gastric tubular adenocarcinoma | Homo sapiens | CVCL_1603 | ||
HGC-27 cells | Gastric carcinoma | Homo sapiens | CVCL_1279 | ||
Response regulation | circRPPH1 promoted the stemness of gastric cancer cells dependent on the miR-375/SLC7A11. This study provides a potential target for gastric cancer progression based on the circRPPH1/miR-375/SLC7A11 regulatory axis. | ||||
Experiment 11 Reporting the Ferroptosis-centered Disease Response by This Target | [22] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Gastric cancer [ICD-11: 2B72] | ||||
Responsed Regulator | PMAN (IncRNA) | Suppressor | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
In Vitro Model | AGS cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0139 | |
MGC-803 cells | Gastric mucinous adenocarcinoma | Homo sapiens | CVCL_5334 | ||
In Vivo Model |
For animal models of gastric subserosal injection, we collected MGC-803 cell lines (5 x 10 cells) that were infected by lentivirus with or without PMAN-OE, and suspended in 40 ul serum-free medium (50% Matrigel). After that, nude mice (six mice per group) were anesthetized by intraperitoneal injection of 100 ul of pentobarbital (1%). After disinfection, the abdominal cavity was opened to expose the greater curvature of the stomach. The tumor suspension (40 ul) was implanted under the serosa of the greater curvature of the stomach of the nude mice through an insulin needle.
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Response regulation | HIF-1 could act as a protective factor against ferroptosis in gastric cancer (GC) cells. HIF-1 activates PMAN at the transcriptional level, which greatly improves the output of ELAVL1 in the cytoplasm. ELAVL1 directly combines with the AREs of SLC7A11 mRNA 3-UTR and improves the stability ofSLC7A11mRNA, thereby increasing the expression of SLC7A11 and reducing the accumulation of ROS and iron in ferroptosis, ultimately promoting the proliferation and development of tumor cells. | ||||
Experiment 12 Reporting the Ferroptosis-centered Disease Response by This Target | [25] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Gastric cancer [ICD-11: 2B72] | ||||
Responsed Regulator | CircRPPH1 (circRNA) | Suppressor | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | MKN45 cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0434 | |
AGS cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0139 | ||
Hs746T cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0333 | ||
NCI-N87 cells | Gastric tubular adenocarcinoma | Homo sapiens | CVCL_1603 | ||
HGC-27 cells | Gastric carcinoma | Homo sapiens | CVCL_1279 | ||
Response regulation | circRPPH1 promoted the stemness of gastric cancer cells dependent on the miR-375/SLC7A11. This study provides a potential target for gastric cancer progression based on the circRPPH1/miR-375/SLC7A11 regulatory axis. | ||||
Voltage-dependent anion-selective channel protein 3 (VDAC3)
In total 2 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [5] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Gastric cancer [ICD-11: 2B72] | ||||
Responsed Regulator | F-box/WD repeat-containing protein 7 (FBXW7) | Driver | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | AGS cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0139 | |
HGC-27 cells | Gastric carcinoma | Homo sapiens | CVCL_1279 | ||
BGC-823 cells | Gastric carcinoma | Homo sapiens | CVCL_3360 | ||
MGC-803 cells | Gastric mucinous adenocarcinoma | Homo sapiens | CVCL_5334 | ||
MKN45 cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0434 | ||
GES-1 cells | Normal | Homo sapiens | CVCL_EQ22 | ||
In Vivo Model |
Four- to six-week-old nude mice (BALB/c) were purchased from Jiangsu Jicui Yaokang Biotechnology Co. Ltd. (Nanjing, China) and then randomly divided into 3 groups (n = 5 per group). PO-BDNF-AS-HGC-27 cells, PONC-BDNF-AS-HGC-27 cells, or PO-BDNF-AS + PO-FBXW7-HGC-27 cells (5 x 106) were suspended in 100 ul DMEM and subcutaneously injected into the flanks of the mice in each group. After 10 days, we measured the tumor size every week using digital Vernier calipers and calculated the tumor volume based on the formula: volume = 1/2 x (width2 x length). On the 30th day or when the tumor became larger than 1.5 cm in diameter, the mice were sacrificed. Subsequently, the subcutaneous graft tumors were removed for further experiments. For the intraabdominal tumor model, we randomly divided the mice into two groups (n = 6 per group). PO-BDNF-AS-HGC-27 cells or PONC-BDNF-AS-HGC-27 cells (8 x 106) were suspended in 150 uL DMEM and intraperitoneally injected into the mice in each group (weight, approximately 18.0-19.0 g). Five weeks after injection, the mice were euthanized and necropsied to assess abdominal tumor burden and tumor location. Finally, we detected the mRNA and protein expression levels of relevant genes in the tumor tissues by RT-PCR and western blotting assays.
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Response regulation | BDNF-AS could regulate FBXW7 expression by recruiting WDR5, thus affecting FBXW7 transcription, and FBXW7 regulated the protein expression of VDAC3 through ubiquitination. Conclusively, our research demonstrated that the BDNF-AS/WDR5/FBXW7 axis regulates ferroptosis in gastric cancer by affecting VDAC3 ubiquitination. | ||||
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target | [5] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Gastric cancer [ICD-11: 2B72] | ||||
Responsed Regulator | BDNF-AS (IncRNA) | Suppressor | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | AGS cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0139 | |
HGC-27 cells | Gastric carcinoma | Homo sapiens | CVCL_1279 | ||
BGC-823 cells | Gastric carcinoma | Homo sapiens | CVCL_3360 | ||
MGC-803 cells | Gastric mucinous adenocarcinoma | Homo sapiens | CVCL_5334 | ||
MKN45 cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0434 | ||
GES-1 cells | Normal | Homo sapiens | CVCL_EQ22 | ||
In Vivo Model |
Four- to six-week-old nude mice (BALB/c) were purchased from Jiangsu Jicui Yaokang Biotechnology Co. Ltd. (Nanjing, China) and then randomly divided into 3 groups (n = 5 per group). PO-BDNF-AS-HGC-27 cells, PONC-BDNF-AS-HGC-27 cells, or PO-BDNF-AS + PO-FBXW7-HGC-27 cells (5 x 106) were suspended in 100 ul DMEM and subcutaneously injected into the flanks of the mice in each group. After 10 days, we measured the tumor size every week using digital Vernier calipers and calculated the tumor volume based on the formula: volume = 1/2 x (width2 x length). On the 30th day or when the tumor became larger than 1.5 cm in diameter, the mice were sacrificed. Subsequently, the subcutaneous graft tumors were removed for further experiments. For the intraabdominal tumor model, we randomly divided the mice into two groups (n = 6 per group). PO-BDNF-AS-HGC-27 cells or PONC-BDNF-AS-HGC-27 cells (8 x 106) were suspended in 150 uL DMEM and intraperitoneally injected into the mice in each group (weight, approximately 18.0-19.0 g). Five weeks after injection, the mice were euthanized and necropsied to assess abdominal tumor burden and tumor location. Finally, we detected the mRNA and protein expression levels of relevant genes in the tumor tissues by RT-PCR and western blotting assays.
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Response regulation | BDNF-AS could regulate FBXW7 expression by recruiting WDR5, thus affecting FBXW7 transcription, and FBXW7 regulated the protein expression of VDAC3 through ubiquitination. Conclusively, our research demonstrated that the BDNF-AS/WDR5/FBXW7 axis regulates ferroptosis in gastric cancer by affecting VDAC3 ubiquitination. | ||||
Unspecific Target
In total 13 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [6] | ||||
Responsed Disease | Gastric cancer [ICD-11: 2B72] | ||||
Responsed Drug | Dexmedetomidine | Approved | |||
Responsed Regulator | Transcription factor E2F7 (E2F7) | Suppressor | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | SNU-1 cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0099 | |
AGS cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0139 | ||
GES-1 cells | Normal | Homo sapiens | CVCL_EQ22 | ||
In Vivo Model |
Female BALB/c nude mice (4-6 weeks old) were obtained from Beijing Institute of Life Sciences (Beijing, China) and the mice were maintained under the standard conditions. AGS cells (2 x 106 cells/mL) were suspended in 100 ul of PBS and were subcutaneously injected in the right flank of mice. After 1 week, mice were divided into four groups (n = 5): Ctrl, 0.5 ug/kg, 1.0 ug/kg, and 2.0 ug/kg groups. The mice were intraperitoneally injected with DEX once a day for 15 days. Mice in the control group were injected with the same amount of normal saline. Tumor size was measured every 2 days and calculated with the formula: 0.5 x length x width2. After the last DEX injection was completed, mice were euthanized with sodium pentobarbital (100 mg/kg) and then sacrificed by decapitation. The tumor tissues were isolated and weighted. Immunohistochemistry for Ki67 and TUNEL assay were performed on paraffin-embedded xenograft tumor tissue sections.
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Response regulation | The current work studied the role of Dexmedetomidine (DEX) in gastric cancer cells and discovered that DEX suppressed GC growth by causing ferroptosis. Furthermore, the circ0008035/miR-302a/E2F7 axis was involved in DEX-induced ferroptotic cell death in GC. | ||||
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target | [6] | ||||
Responsed Disease | Gastric cancer [ICD-11: 2B72] | ||||
Responsed Drug | Dexmedetomidine | Approved | |||
Responsed Regulator | Circ_0008035 (circRNA) | Suppressor | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | SNU-1 cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0099 | |
AGS cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0139 | ||
GES-1 cells | Normal | Homo sapiens | CVCL_EQ22 | ||
In Vivo Model |
Female BALB/c nude mice (4-6 weeks old) were obtained from Beijing Institute of Life Sciences (Beijing, China) and the mice were maintained under the standard conditions. AGS cells (2 x 106 cells/mL) were suspended in 100 ul of PBS and were subcutaneously injected in the right flank of mice. After 1 week, mice were divided into four groups (n = 5): Ctrl, 0.5 ug/kg, 1.0 ug/kg, and 2.0 ug/kg groups. The mice were intraperitoneally injected with DEX once a day for 15 days. Mice in the control group were injected with the same amount of normal saline. Tumor size was measured every 2 days and calculated with the formula: 0.5 x length x width2. After the last DEX injection was completed, mice were euthanized with sodium pentobarbital (100 mg/kg) and then sacrificed by decapitation. The tumor tissues were isolated and weighted. Immunohistochemistry for Ki67 and TUNEL assay were performed on paraffin-embedded xenograft tumor tissue sections.
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Response regulation | The current work studied the role of Dexmedetomidine (DEX) in Gastric cancer (GC) cells and discovered that DEX suppressed GC growth by causing ferroptosis. Furthermore, the circ0008035/miR-302a/E2F7 axis was involved in DEX-induced ferroptotic cell death in GC. | ||||
Experiment 3 Reporting the Ferroptosis-centered Disease Response by This Target | [6] | ||||
Responsed Disease | Gastric cancer [ICD-11: 2B72] | ||||
Responsed Drug | Dexmedetomidine | Approved | |||
Responsed Regulator | hsa-mir-302a (Precursor RNA) | Driver | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | SNU-1 cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0099 | |
AGS cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0139 | ||
GES-1 cells | Normal | Homo sapiens | CVCL_EQ22 | ||
In Vivo Model |
Female BALB/c nude mice (4-6 weeks old) were obtained from Beijing Institute of Life Sciences (Beijing, China) and the mice were maintained under the standard conditions. AGS cells (2 x 106 cells/mL) were suspended in 100 ul of PBS and were subcutaneously injected in the right flank of mice. After 1 week, mice were divided into four groups (n = 5): Ctrl, 0.5 ug/kg, 1.0 ug/kg, and 2.0 ug/kg groups. The mice were intraperitoneally injected with DEX once a day for 15 days. Mice in the control group were injected with the same amount of normal saline. Tumor size was measured every 2 days and calculated with the formula: 0.5 x length x width2. After the last DEX injection was completed, mice were euthanized with sodium pentobarbital (100 mg/kg) and then sacrificed by decapitation. The tumor tissues were isolated and weighted. Immunohistochemistry for Ki67 and TUNEL assay were performed on paraffin-embedded xenograft tumor tissue sections.
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Response regulation | The current work studied the role of Dexmedetomidine (DEX) in Gastric cancer (GC) cells and discovered that DEX suppressed GC growth by causing ferroptosis. Furthermore, the circ0008035/miR-302a/E2F7 axis was involved in DEX-induced ferroptotic cell death in GC. | ||||
Experiment 4 Reporting the Ferroptosis-centered Disease Response by This Target | [7] | ||||
Responsed Disease | Gastric cancer [ICD-11: 2B72] | ||||
Responsed Drug | Amentoflavone | Investigative | |||
Responsed Regulator | Cyclic AMP-dependent transcription factor ATF-2 (ATF2) | Suppressor | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
In Vitro Model | GSE-1 (Human gastric mucosal epithelial cells) | ||||
AGS cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0139 | ||
HGC-27 cells | Gastric carcinoma | Homo sapiens | CVCL_1279 | ||
In Vivo Model |
The BALB/c nude mice (n = 15, 4-6 weeks old) were purchased from Charles River Labs and kept under controlled conditions. Then 1 x 106 AGS cells were inoculated subcutaneously into nude mice. When the tumor reached to 100 mm3, mice were randomly divided into three groups, the control group was intraperitoneally injected with saline, the AF group was intraperitoneally injected with AF at dosages of 80 mg/kg/day, and AF + anti-miR-496 group received intraperitoneal injection, followed by the administration of miR-496 antagonist via intra-tumor injection once a week for 4 weeks.
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Response regulation | Amentoflavone suppressed the proliferation and induced ferroptotic cell death in gastric cancer cells via miR-496/ATF2 axis, indicating a novel therapeutic approach for GC patients. | ||||
Experiment 5 Reporting the Ferroptosis-centered Disease Response by This Target | [7] | ||||
Responsed Disease | Gastric cancer [ICD-11: 2B72] | ||||
Responsed Drug | Amentoflavone | Investigative | |||
Responsed Regulator | hsa-miR-496 (miRNA) | Driver | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
In Vitro Model | GSE-1 (Human gastric mucosal epithelial cells) | ||||
AGS cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0139 | ||
HGC-27 cells | Gastric carcinoma | Homo sapiens | CVCL_1279 | ||
In Vivo Model |
The BALB/c nude mice (n = 15, 4-6 weeks old) were purchased from Charles River Labs and kept under controlled conditions. Then 1 x 106 AGS cells were inoculated subcutaneously into nude mice. When the tumor reached to 100 mm3, mice were randomly divided into three groups, the control group was intraperitoneally injected with saline, the AF group was intraperitoneally injected with AF at dosages of 80 mg/kg/day, and AF + anti-miR-496 group received intraperitoneal injection, followed by the administration of miR-496 antagonist via intra-tumor injection once a week for 4 weeks.
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Response regulation | Amentoflavone suppressed the proliferation and induced ferroptotic cell death in gastric cancer cells via miR-496/ATF2 axis, indicating a novel therapeutic approach for GC patients. | ||||
Experiment 6 Reporting the Ferroptosis-centered Disease Response by This Target | [8] | ||||
Responsed Disease | Gastric cancer [ICD-11: 2B72] | ||||
Responsed Drug | Polyphyllin B | Investigative | |||
Responsed Regulator | Microtubule-associated proteins 1A/1B light chain 3B {ECO:0000305} (MAP1LC3B) | Driver | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Cell Process | Cell ferroptosis | ||||
Cell apoptosis | |||||
Cell proliferation | |||||
In Vitro Model | NUGC-3 cells | Gastric carcinoma | Homo sapiens | CVCL_1612 | |
MKN-1 cells | Gastric carcinoma | Homo sapiens | CVCL_1415 | ||
MKN45 cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0434 | ||
HGC-27 cells | Gastric carcinoma | Homo sapiens | CVCL_1279 | ||
NUGC-4 cells | Gastric signet ring cell adenocarcinoma | Homo sapiens | CVCL_3082 | ||
In Vivo Model |
The nude mice were raised in our laboratory for a week before the experiment. Then, 5 x 106 MKN-1 cells were subcutaneously injected to establish the subcutaneous xenograft tumour model in nude mice. When the maximum diameter of the xenograft tumours grew steadily to 1 cm, they were dissected completely and cut into 1 mm3 tissue fragments. Then, the tissue fragment was inserted into the surface of the serosa on the greater curvature of the stomach. Different doses of PB (2.5 mg/kg or 5.0 mg/kg) were given by intraperitoneal injection once a day for 3 weeks. The control group was given the same volume of vehicle. The positive control group was given 5-Fu at the dose of 10 mg/kg. The body weight and tumour size of nude mice were recorded. Mice were administered fluorescein substrate (150 mg/kg) intraperitoneally for in vivo imaging twice a week on a Xenogen IVIS 200 imaging system (Caliper Life Sciences, USA). The tumour inhibition rate was analysed using LT Living Image 4.3 Software.
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Response regulation | We identified a novel GPx4 inhibitor, polyphyllin B (PB), which can induce ferroptosis by down-regulating GPx4 expression in gastric cancer cells. It has also been shown to inhibit cell proliferation, suppress invasion and migration, induce apoptosis, and block the cell cycle progression in GC cellsin vitro. Then, immunofluorescence and western blotting assay confirmed that PB can regulate the expression of LC3B, TFR1, NOCA4 and FTH1in vitro, which suggested that suggest that PB may increase the level of Fe2+by transporting Fe3+into the cell by TFR1 and promoting NCOA4-dependent iron autophagy. | ||||
Experiment 7 Reporting the Ferroptosis-centered Disease Response by This Target | [26] | ||||
Responsed Disease | Gastric cancer [ICD-11: 2B72] | ||||
Responsed Regulator | ADP-ribosylation factor 6 (ARF6) | Suppressor | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Ras signaling pathway | hsa04014 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
In Vitro Model | GES-1 cells | Normal | Homo sapiens | CVCL_EQ22 | |
SGC-7901 cells | Gastric carcinoma | Homo sapiens | CVCL_0520 | ||
BGC-823 cells | Gastric carcinoma | Homo sapiens | CVCL_3360 | ||
AGS cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0139 | ||
MKN45 cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0434 | ||
SNU-1 cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0099 | ||
MGC-803 cells | Gastric mucinous adenocarcinoma | Homo sapiens | CVCL_5334 | ||
Response regulation | ARF6, as a downstream effector of the Kirsten rat sarcoma viral oncogene (Kras)/extracellular signal-regulated kinases (ERK) signaling pathway, may increase proliferation and induce the Warburg effect in gastric cancer (GC) cells. ARF6 may control capecitabine resistance via several routes. | ||||
Experiment 8 Reporting the Ferroptosis-centered Disease Response by This Target | [27] | ||||
Responsed Disease | Gastric cancer [ICD-11: 2B72] | ||||
Responsed Regulator | Circ_0000190 (circRNA) | Driver | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
Cell migration | |||||
Cell invasion | |||||
In Vitro Model | AGS cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0139 | |
KATO III cells | Gastric signet ring cell adenocarcinoma | Homo sapiens | CVCL_0371 | ||
MKN-1 cells | Gastric carcinoma | Homo sapiens | CVCL_1415 | ||
HGC-27 cells | Gastric carcinoma | Homo sapiens | CVCL_1279 | ||
In Vivo Model |
Nude mice (5-week old; Shanghai SLAC Laboratory Animals, Shanghai, China) were arbitrarily divided into two groups (n = 5). AGS cells (1 x 106 ) stably expressing circ_0000190 were inoculated into the flank of the nude mice. Tumor volume was monitored every 4 d with the method of (length x width2 )/2. These mice were euthanized after 28-d inoculation.
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Response regulation | Circ_0000190 overexpression inhibited the proliferation, migration and invasion and promoted Erastin- or ras selective lethal 3 (RSL3)-mediated ferroptosis in gastric cancer cells. And circ_0000190 suppressed GC progression via miR-382-5p-dependent regulation of ZNRF3. | ||||
Experiment 9 Reporting the Ferroptosis-centered Disease Response by This Target | [28] | ||||
Responsed Disease | Gastric cancer [ICD-11: 2B72] | ||||
Responsed Regulator | Cadherin-1 (CDH1) | Suppressor | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Hippo signaling pathway | hsa04390 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
In Vitro Model | SNU-16 cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0076 | |
HEK-293T cells | Normal | Homo sapiens | CVCL_0063 | ||
SNU-668 cells | Gastric signet ring cell adenocarcinoma | Homo sapiens | CVCL_5081 | ||
In Vivo Model |
7.5 X 106 SNU16 sgCDH1 cells expressing a vector, wild-type E-cadherin, or the D291N mutant in 100 ul 1:1 Matrigel: serum-free RPMI were injected into the left flank of athymicnu/numice (Envigo). Tumor growth was monitored every 3 days by caliper. Once tumors reached a mean volume of 150 mm3, mice with each tumor type were randomly grouped into two groups. IKE (MedChemExpress) was resuspended in a solution of 65% D5W (5% dextrose in water), 5% Tween-80, and 30% PEG-400. Mice were then treated daily with either 40 mg/kg IKE or the vehicle via i.p. injection.
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Response regulation | E-cadherin (CDH1) is a biomarker predicting the sensitivity to ferroptosis of diffuse-type gastric cancer (DGC) cells, both in primary tumor tissue and in circulation, thus guiding the usage of future ferroptosis-inducing therapeutics for the treatment of DGC. | ||||
Experiment 10 Reporting the Ferroptosis-centered Disease Response by This Target | [27] | ||||
Responsed Disease | Gastric cancer [ICD-11: 2B72] | ||||
Responsed Regulator | E3 ubiquitin-protein ligase ZNRF3 (ZNRF3) | Driver | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
Cell migration | |||||
Cell invasion | |||||
In Vitro Model | AGS cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0139 | |
KATO III cells | Gastric signet ring cell adenocarcinoma | Homo sapiens | CVCL_0371 | ||
MKN-1 cells | Gastric carcinoma | Homo sapiens | CVCL_1415 | ||
HGC-27 cells | Gastric carcinoma | Homo sapiens | CVCL_1279 | ||
In Vivo Model |
Nude mice (5-week old; Shanghai SLAC Laboratory Animals, Shanghai, China) were arbitrarily divided into two groups (n = 5). AGS cells (1 x 106 ) stably expressing circ_0000190 were inoculated into the flank of the nude mice. Tumor volume was monitored every 4 d with the method of (length x width2 )/2. These mice were euthanized after 28-d inoculation.
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Response regulation | Circ_0000190 overexpression inhibited the proliferation, migration and invasion and promoted Erastin- or ras selective lethal 3 (RSL3)-mediated ferroptosis in gastric cancer cells. And circ_0000190 suppressed GC progression via miR-382-5p-dependent regulation of ZNRF3. | ||||
Experiment 11 Reporting the Ferroptosis-centered Disease Response by This Target | [27] | ||||
Responsed Disease | Gastric cancer [ICD-11: 2B72] | ||||
Responsed Regulator | hsa-miR-382-5p (miRNA) | Suppressor | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
Cell migration | |||||
Cell invasion | |||||
In Vitro Model | AGS cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0139 | |
KATO III cells | Gastric signet ring cell adenocarcinoma | Homo sapiens | CVCL_0371 | ||
MKN-1 cells | Gastric carcinoma | Homo sapiens | CVCL_1415 | ||
HGC-27 cells | Gastric carcinoma | Homo sapiens | CVCL_1279 | ||
In Vivo Model |
Nude mice (5-week old; Shanghai SLAC Laboratory Animals, Shanghai, China) were arbitrarily divided into two groups (n = 5). AGS cells (1 x 106 ) stably expressing circ_0000190 were inoculated into the flank of the nude mice. Tumor volume was monitored every 4 d with the method of (length x width2 )/2. These mice were euthanized after 28-d inoculation.
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Response regulation | Circ_0000190 overexpression inhibited the proliferation, migration and invasion and promoted Erastin- or ras selective lethal 3 (RSL3)-mediated ferroptosis in gastric cancer cells. And circ_0000190 suppressed GC progression via miR-382-5p-dependent regulation of ZNRF3. | ||||
Experiment 12 Reporting the Ferroptosis-centered Disease Response by This Target | [29] | ||||
Responsed Disease | Gastric cancer [ICD-11: 2B72] | ||||
Responsed Regulator | Elongation of very long chain fatty acids protein 5 (ELOVL5) | Driver | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | AGS cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0139 | |
MKN-28 cells | Gastric epithelial carcinoma | Homo sapiens | CVCL_1416 | ||
MKN45 cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0434 | ||
NCI-N87 cells | Gastric tubular adenocarcinoma | Homo sapiens | CVCL_1603 | ||
SNU-484 cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0100 | ||
SNU-601 cells | Gastric signet ring cell adenocarcinoma | Homo sapiens | CVCL_0101 | ||
SNU-668 cells | Gastric signet ring cell adenocarcinoma | Homo sapiens | CVCL_5081 | ||
SNU-719 cells | Gastric tubular adenocarcinoma | Homo sapiens | CVCL_5086 | ||
YCC-6 cells | Gastric adenocarcinoma | Homo sapiens | CVCL_9662 | ||
YCC-16 cells | Gastric adenocarcinoma | Homo sapiens | CVCL_9649 | ||
Hs746T cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0333 | ||
Response regulation | The expression of elongation of very long-chain fatty acid protein 5 (ELOVL5) and fatty acid desaturase 1 (FADS1) is up-regulated in mesenchymal-type gastric cancer cells (GCs), leading to ferroptosis sensitization. | ||||
Experiment 13 Reporting the Ferroptosis-centered Disease Response by This Target | [29] | ||||
Responsed Disease | Gastric cancer [ICD-11: 2B72] | ||||
Responsed Regulator | Acyl-CoA (8-3)-desaturase (FADS1) | Driver | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | AGS cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0139 | |
MKN-28 cells | Gastric epithelial carcinoma | Homo sapiens | CVCL_1416 | ||
MKN45 cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0434 | ||
NCI-N87 cells | Gastric tubular adenocarcinoma | Homo sapiens | CVCL_1603 | ||
SNU-484 cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0100 | ||
SNU-601 cells | Gastric signet ring cell adenocarcinoma | Homo sapiens | CVCL_0101 | ||
SNU-668 cells | Gastric signet ring cell adenocarcinoma | Homo sapiens | CVCL_5081 | ||
SNU-719 cells | Gastric tubular adenocarcinoma | Homo sapiens | CVCL_5086 | ||
YCC-6 cells | Gastric adenocarcinoma | Homo sapiens | CVCL_9662 | ||
YCC-16 cells | Gastric adenocarcinoma | Homo sapiens | CVCL_9649 | ||
Hs746T cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0333 | ||
Response regulation | The expression of elongation of very long-chain fatty acid protein 5 (ELOVL5) and fatty acid desaturase 1 (FADS1) is up-regulated in mesenchymal-type gastric cancer cells (GCs), leading to ferroptosis sensitization. | ||||
Transferrin receptor protein 1 (TFRC)
In total 1 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [8] | ||||
Target for Ferroptosis | Driver | ||||
Responsed Disease | Gastric cancer [ICD-11: 2B72] | ||||
Responsed Drug | Polyphyllin B | Investigative | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Cell Process | Cell ferroptosis | ||||
Cell apoptosis | |||||
Cell proliferation | |||||
In Vitro Model | NUGC-3 cells | Gastric carcinoma | Homo sapiens | CVCL_1612 | |
MKN-1 cells | Gastric carcinoma | Homo sapiens | CVCL_1415 | ||
MKN45 cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0434 | ||
HGC-27 cells | Gastric carcinoma | Homo sapiens | CVCL_1279 | ||
NUGC-4 cells | Gastric signet ring cell adenocarcinoma | Homo sapiens | CVCL_3082 | ||
In Vivo Model |
The nude mice were raised in our laboratory for a week before the experiment. Then, 5 x 106 MKN-1 cells were subcutaneously injected to establish the subcutaneous xenograft tumour model in nude mice. When the maximum diameter of the xenograft tumours grew steadily to 1 cm, they were dissected completely and cut into 1 mm3 tissue fragments. Then, the tissue fragment was inserted into the surface of the serosa on the greater curvature of the stomach. Different doses of PB (2.5 mg/kg or 5.0 mg/kg) were given by intraperitoneal injection once a day for 3 weeks. The control group was given the same volume of vehicle. The positive control group was given 5-Fu at the dose of 10 mg/kg. The body weight and tumour size of nude mice were recorded. Mice were administered fluorescein substrate (150 mg/kg) intraperitoneally for in vivo imaging twice a week on a Xenogen IVIS 200 imaging system (Caliper Life Sciences, USA). The tumour inhibition rate was analysed using LT Living Image 4.3 Software.
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Response regulation | We identified a novel GPx4 inhibitor, polyphyllin B (PB), which can induce ferroptosis by down-regulating GPx4 expression in gastric cancer cells. It has also been shown to inhibit cell proliferation, suppress invasion and migration, induce apoptosis, and block the cell cycle progression in GC cellsin vitro. Then, immunofluorescence and western blotting assay confirmed that PB can regulate the expression of LC3B, TFR1, NOCA4 and FTH1in vitro, which suggested that suggest that PB may increase the level of Fe2+by transporting Fe3+into the cell by TFR1 and promoting NCOA4-dependent iron autophagy. | ||||
Prostaglandin G/H synthase 2 (PTGS2)
In total 2 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [4] | ||||
Target for Ferroptosis | Marker | ||||
Responsed Disease | Gastric cancer [ICD-11: 2B72] | ||||
Responsed Drug | Tanshinone IIA | Investigative | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
In Vitro Model | BGC-823 cells | Gastric carcinoma | Homo sapiens | CVCL_3360 | |
NCI-N87 cells | Gastric tubular adenocarcinoma | Homo sapiens | CVCL_1603 | ||
In Vivo Model |
All mice were housed under a setting of 12-h light/dark cycle at 22 ± 1, 55% humidity and fed with water and food provided at regular time. During the entire maintenance period, all mice were permitted free cage activity without joint immobilization. The initial body weights of the mice were between 20 and 23 grams. After subcutaneous injection of 2 x 106 BGC-823 gastric cancer cells into the back of NOD-SCID mice, the mice were treated with or without Tan IIA (50 mg/kg) or Tan IIA in combination with Fer-1 (50 mg/kg). Tan IIA was diluted in DMSO:Methanol:Hydroxypropyl-b-cydodextrin (HP-b-CD) = 1:1:1. Fer-1 was also dissolved in DMSO:Methanol:HP-b-CD. Seven days after BGC-823 gastric cancer cells injection, intraperitoneal injection with Tan IIA was carried out every other day followed by killing at day 22 of tumor cell inoculation. All mice were killed by dislocation of the cervical vertebrae. Before killing, the tumor volume was measured every 3 days. All experiments were carried out using six mice each group in three independent experiments of a time-dependent manner with three time points.
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Response regulation | Tanshinone IIA increased lipid peroxidation and up-regulated Ptgs2 and Chac1 expression, two markers of ferroptosis. In addition, Tan IIA also up-regulated p53 expression and down-regulated xCT expression. Therefore, Tan IIA could suppress the proliferation of gastric cancer via inducing p53 upregulation-mediated ferroptosis. | ||||
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target | [9] | ||||
Target for Ferroptosis | Marker | ||||
Responsed Disease | Gastric cancer [ICD-11: 2B72] | ||||
Responsed Drug | XN4 | Investigative | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | SGC-7901 cells | Gastric carcinoma | Homo sapiens | CVCL_0520 | |
BGC-823 cells | Gastric carcinoma | Homo sapiens | CVCL_3360 | ||
GES-1 cells | Normal | Homo sapiens | CVCL_EQ22 | ||
Response regulation | The pro-ferroptotic role of XN4 in gastric cancer (GC) might enable it to become a promising drug for GC treatment in the future despite the need for extensive research. Moreover, GPX4 levels decreased, but NOX4 and ferroptosis-related protein PTGS2 levels increased in GC cells following XN4 treatment, which was nullified by NOX4 knockdown. | ||||
Nuclear receptor coactivator 4 (NCOA4)
In total 1 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [8] | ||||
Target for Ferroptosis | Driver | ||||
Responsed Disease | Gastric cancer [ICD-11: 2B72] | ||||
Responsed Drug | Polyphyllin B | Investigative | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Cell Process | Cell ferroptosis | ||||
Cell apoptosis | |||||
Cell proliferation | |||||
In Vitro Model | NUGC-3 cells | Gastric carcinoma | Homo sapiens | CVCL_1612 | |
MKN-1 cells | Gastric carcinoma | Homo sapiens | CVCL_1415 | ||
MKN45 cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0434 | ||
HGC-27 cells | Gastric carcinoma | Homo sapiens | CVCL_1279 | ||
NUGC-4 cells | Gastric signet ring cell adenocarcinoma | Homo sapiens | CVCL_3082 | ||
In Vivo Model |
The nude mice were raised in our laboratory for a week before the experiment. Then, 5 x 106 MKN-1 cells were subcutaneously injected to establish the subcutaneous xenograft tumour model in nude mice. When the maximum diameter of the xenograft tumours grew steadily to 1 cm, they were dissected completely and cut into 1 mm3 tissue fragments. Then, the tissue fragment was inserted into the surface of the serosa on the greater curvature of the stomach. Different doses of PB (2.5 mg/kg or 5.0 mg/kg) were given by intraperitoneal injection once a day for 3 weeks. The control group was given the same volume of vehicle. The positive control group was given 5-Fu at the dose of 10 mg/kg. The body weight and tumour size of nude mice were recorded. Mice were administered fluorescein substrate (150 mg/kg) intraperitoneally for in vivo imaging twice a week on a Xenogen IVIS 200 imaging system (Caliper Life Sciences, USA). The tumour inhibition rate was analysed using LT Living Image 4.3 Software.
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Response regulation | We identified a novel GPx4 inhibitor, polyphyllin B (PB), which can induce ferroptosis by down-regulating GPx4 expression in gastric cancer cells. It has also been shown to inhibit cell proliferation, suppress invasion and migration, induce apoptosis, and block the cell cycle progression in GC cellsin vitro. Then, immunofluorescence and western blotting assay confirmed that PB can regulate the expression of LC3B, TFR1, NOCA4 and FTH1in vitro, which suggested that suggest that PB may increase the level of Fe2+by transporting Fe3+into the cell by TFR1 and promoting NCOA4-dependent iron autophagy. | ||||
Nuclear factor erythroid 2-related factor 2 (NFE2L2)
In total 1 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [17] | ||||
Target for Ferroptosis | Marker/Suppressor | ||||
Responsed Disease | Gastric cancer [ICD-11: 2B72] | ||||
Responsed Drug | Polyphyllin I | Investigative | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | MKN45 cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0434 | |
AGS cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0139 | ||
In Vivo Model |
A subcutaneous gastric tumor model was established by subcutaneously injecting 1 x 106 AGS cells or 2 x 106 MKN-45 cells near the right axilla of mice. Seven days after tumor cell inoculation, mice received daily i. p. Injection of PPI (3 mg/kg, dissolved in 1% DMSO + 5% PEG300 + 5% Tween 80 + 89% deionized water), as described previously, or the control solution with the same solvent. Mice were weighed at day 15, while tumor volumes were measured every 3 days and calculated using a formula: length x width2/2.
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Response regulation | For the first time, our results have demonstrated that Polyphyllin I exerts its antitumor activity on the gastric cancer by, at least partially, inducing cancer cell ferroptosisviaregulating NRF2/FTH1 pathway. | ||||
NADPH oxidase 4 (NOX4)
In total 1 item(s) under this target | ||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [9] | |||
Target for Ferroptosis | Driver | |||
Responsed Disease | Gastric cancer [ICD-11: 2B72] | |||
Responsed Drug | XN4 | Investigative | ||
Pathway Response | Fatty acid metabolism | hsa01212 | ||
Ferroptosis | hsa04216 | |||
Cell Process | Cell ferroptosis | |||
In Vitro Model | SGC-7901 cells | Gastric carcinoma | Homo sapiens | CVCL_0520 |
BGC-823 cells | Gastric carcinoma | Homo sapiens | CVCL_3360 | |
GES-1 cells | Normal | Homo sapiens | CVCL_EQ22 | |
Response regulation | The pro-ferroptotic role of XN4 in gastric cancer (GC) might enable it to become a promising drug for GC treatment in the future despite the need for extensive research. Moreover, GPX4 levels decreased, but NOX4 and ferroptosis-related protein PTGS2 levels increased in GC cells following XN4 treatment, which was nullified by NOX4 knockdown. | |||
Long-chain-fatty-acid--CoA ligase 4 (ACSL4)
In total 2 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [18] | ||||
Target for Ferroptosis | Driver | ||||
Responsed Disease | Gastric cancer [ICD-11: 2B72] | ||||
Responsed Regulator | Cystathionine beta-synthase (CBS) | Suppressor | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Fatty acid metabolism | hsa01212 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | MKN45 cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0434 | |
MKN-28 cells | Gastric epithelial carcinoma | Homo sapiens | CVCL_1416 | ||
In Vivo Model |
Female non-obese diabetic severe combined immune-deficient mice at 5 weeks of age were divided into indicated groups and injected subcutaneously at either side of flank area with indicated cell lines (1 x 106 cells) suspended in 0.1 ml phosphate-buffered saline (PBS). Tumor sizes in all groups were measured every 3 days using Vernier calipers and calculated using the following formula: (length x width2)/2. For the xenograft Cisplatin treatment assay, day 0 was designed when tumors reached around 50 mm3 in volume. DDP 7 mg/kg or carrier (PBS, 100 uL)) was injected intraperitoneally 1 time per week. 21 days after treatment, all mice were sacrificed and tumors were harvested and weighed. Representative images were presented, and all experiments were repeated at least 3 times.
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Response regulation | Schematic diagram showing that HIF-1 induces lncRNA-CBSLR to recruit YTHDF2 protein and CBS mRNA to form CBSLR/ YTHDF2/CBS complex, which in turn decreases CBS mRNA stability in an m6A dependent manner. The decreased CBS expression reduced methylation of ACSL4 protein, thus, the protein is degraded via the ubiquitination-proteasome pathway. Hypoxia inducible lncRNA-CBSLR modulates ferroptosis through m6A-YTHDF2-dependent modulation of CBS in gastric cancer. | ||||
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target | [18] | ||||
Target for Ferroptosis | Driver | ||||
Responsed Disease | Gastric cancer [ICD-11: 2B72] | ||||
Responsed Regulator | CBSLR (IncRNA) | Driver | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Fatty acid metabolism | hsa01212 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | MKN45 cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0434 | |
MKN-28 cells | Gastric epithelial carcinoma | Homo sapiens | CVCL_1416 | ||
In Vivo Model |
Female non-obese diabetic severe combined immune-deficient mice at 5 weeks of age were divided into indicated groups and injected subcutaneously at either side of flank area with indicated cell lines (1 x 106 cells) suspended in 0.1 ml phosphate-buffered saline (PBS). Tumor sizes in all groups were measured every 3 days using Vernier calipers and calculated using the following formula: (length x width2)/2. For the xenograft Cisplatin treatment assay, day 0 was designed when tumors reached around 50 mm3 in volume. DDP 7 mg/kg or carrier (PBS, 100 uL)) was injected intraperitoneally 1 time per week. 21 days after treatment, all mice were sacrificed and tumors were harvested and weighed. Representative images were presented, and all experiments were repeated at least 3 times.
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Response regulation | Schematic diagram showing that HIF-1 induces lncRNA-CBSLR to recruit YTHDF2 protein and CBS mRNA to form CBSLR/ YTHDF2/CBS complex, which in turn decreases CBS mRNA stability in an m6A dependent manner. The decreased CBS expression reduced methylation of ACSL4 protein, thus, the protein is degraded via the ubiquitination-proteasome pathway. Hypoxia inducible lncRNA-CBSLR modulates ferroptosis through m6A-YTHDF2-dependent modulation of CBS in gastric cancer. | ||||
Heme oxygenase 1 (HMOX1)
In total 1 item(s) under this target | ||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [19] | |||
Target for Ferroptosis | Driver/Suppressor | |||
Responsed Disease | Gastric cancer [ICD-11: 2B72] | |||
Responsed Drug | Andrographis | Approved | ||
Pathway Response | Fatty acid metabolism | hsa01212 | ||
Apoptosis | hsa04210 | |||
Cell Process | Cell ferroptosis | |||
Cell apoptosis | ||||
Cell proliferation | ||||
In Vitro Model | MKN74 cells | Gastric tubular adenocarcinoma | Homo sapiens | CVCL_2791 |
NUGC-4 cells | Gastric signet ring cell adenocarcinoma | Homo sapiens | CVCL_3082 | |
Response regulation | Andrographis exerted antitumor effects in gastric cancer cell lines (MKN74 and NUGC4) by inhibiting proliferation, reducing colony formation and enhancing apoptotic activity. Moreover, andrographis treatment altered the expression of ferroptosis-associated genes, including HMOX1, GCLC, and GCLM. | |||
Glutathione-specific gamma-glutamylcyclotransferase 1 (CHAC1)
In total 2 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [4] | ||||
Target for Ferroptosis | Marker/Driver | ||||
Responsed Disease | Gastric cancer [ICD-11: 2B72] | ||||
Responsed Drug | Tanshinone IIA | Investigative | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
In Vitro Model | BGC-823 cells | Gastric carcinoma | Homo sapiens | CVCL_3360 | |
NCI-N87 cells | Gastric tubular adenocarcinoma | Homo sapiens | CVCL_1603 | ||
In Vivo Model |
All mice were housed under a setting of 12-h light/dark cycle at 22 ± 1, 55% humidity and fed with water and food provided at regular time. During the entire maintenance period, all mice were permitted free cage activity without joint immobilization. The initial body weights of the mice were between 20 and 23 grams. After subcutaneous injection of 2 x 106 BGC-823 gastric cancer cells into the back of NOD-SCID mice, the mice were treated with or without Tan IIA (50 mg/kg) or Tan IIA in combination with Fer-1 (50 mg/kg). Tan IIA was diluted in DMSO:Methanol:Hydroxypropyl-b-cydodextrin (HP-b-CD) = 1:1:1. Fer-1 was also dissolved in DMSO:Methanol:HP-b-CD. Seven days after BGC-823 gastric cancer cells injection, intraperitoneal injection with Tan IIA was carried out every other day followed by killing at day 22 of tumor cell inoculation. All mice were killed by dislocation of the cervical vertebrae. Before killing, the tumor volume was measured every 3 days. All experiments were carried out using six mice each group in three independent experiments of a time-dependent manner with three time points.
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Response regulation | Tanshinone IIA increased lipid peroxidation and up-regulated Ptgs2 and Chac1 expression, two markers of ferroptosis. In addition, Tan IIA also up-regulated p53 expression and down-regulated xCT expression. Therefore, Tan IIA could suppress the proliferation of gastric cancer via inducing p53 upregulation-mediated ferroptosis. | ||||
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target | [20] | ||||
Target for Ferroptosis | Marker/Driver | ||||
Responsed Disease | Gastric cancer [ICD-11: 2B72] | ||||
Responsed Regulator | Cytoplasmic polyadenylation element-binding protein 1 (CPEB1) | Driver | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
In Vitro Model | AGS cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0139 | |
SNU-1 cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0099 | ||
Hs746T cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0333 | ||
HGC-27 cells | Gastric carcinoma | Homo sapiens | CVCL_1279 | ||
GES-1 cells | Normal | Homo sapiens | CVCL_EQ22 | ||
In Vivo Model |
Healthy male nude mice for 5 weeks were randomly divided into four groups, namely: A: Lv-NC + Vehicle group, B: Lv-NC + Erastin group, C: Lv-exCPEB1 + Vehicle group, and D: Lv-exCPEB1 + Erastin group. The living environment of nude mice in each group was 12 h light and 12 h dark, the temperature was 22 ± 1, the humidity was 45-55%. The model was established 1 week after adaptive feeding. GC cells (1 x 106) with stable overexpression of CPEB1 at the logarithmic growth stage were selected and injected subcutaneously in nude mice. When the tumor volume reached 100 mm3, nude mice in groups B and D were injected intraperitoneally with Erastin (30 mg/kg) twice a day (morning and night, respectively), and the tumor tissue diameter and volume were measured and calculated every 3 days after administration.
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Response regulation | CPEB1 overexpression reduced the expression of twist1, an inhibitor of activating transcription factor 4 (ATF4), thereby activating the ATF4/ChaC Glutathione Specific Gamma-Glutamylcyclotransferase 1 (CHAC1) pathway (CHAC1, a molecule known to induce GSH degradation). Furthermore, re-expression of twist1 in gastric cancer cells impaired the effects of CPEB1 overexpression in presence of erastin. | ||||
Glutamate--cysteine ligase regulatory subunit (GCLM)
In total 1 item(s) under this target | ||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [19] | |||
Target for Ferroptosis | Suppressor | |||
Responsed Disease | Gastric cancer [ICD-11: 2B72] | |||
Responsed Drug | Andrographis | Approved | ||
Pathway Response | Fatty acid metabolism | hsa01212 | ||
Apoptosis | hsa04210 | |||
Cell Process | Cell ferroptosis | |||
Cell apoptosis | ||||
Cell proliferation | ||||
In Vitro Model | MKN74 cells | Gastric tubular adenocarcinoma | Homo sapiens | CVCL_2791 |
NUGC-4 cells | Gastric signet ring cell adenocarcinoma | Homo sapiens | CVCL_3082 | |
Response regulation | Andrographis exerted antitumor effects in gastric cancer cell lines (MKN74 and NUGC4) by inhibiting proliferation, reducing colony formation and enhancing apoptotic activity. Moreover, andrographis treatment altered the expression of ferroptosis-associated genes, including HMOX1, GCLC, and GCLM. | |||
Glutamate--cysteine ligase catalytic subunit (GCLC)
In total 1 item(s) under this target | ||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [19] | |||
Target for Ferroptosis | Suppressor | |||
Responsed Disease | Gastric cancer [ICD-11: 2B72] | |||
Responsed Drug | Andrographis | Approved | ||
Pathway Response | Fatty acid metabolism | hsa01212 | ||
Apoptosis | hsa04210 | |||
Cell Process | Cell ferroptosis | |||
Cell apoptosis | ||||
Cell proliferation | ||||
In Vitro Model | MKN74 cells | Gastric tubular adenocarcinoma | Homo sapiens | CVCL_2791 |
NUGC-4 cells | Gastric signet ring cell adenocarcinoma | Homo sapiens | CVCL_3082 | |
Response regulation | Andrographis exerted antitumor effects in gastric cancer cell lines (MKN74 and NUGC4) by inhibiting proliferation, reducing colony formation and enhancing apoptotic activity. Moreover, andrographis treatment altered the expression of ferroptosis-associated genes, including HMOX1, GCLC, and GCLM. | |||
Ferritin heavy chain (FTH1)
In total 2 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [8] | ||||
Target for Ferroptosis | Marker | ||||
Responsed Disease | Gastric cancer [ICD-11: 2B72] | ||||
Responsed Drug | Polyphyllin B | Investigative | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Cell Process | Cell ferroptosis | ||||
Cell apoptosis | |||||
Cell proliferation | |||||
In Vitro Model | NUGC-3 cells | Gastric carcinoma | Homo sapiens | CVCL_1612 | |
MKN-1 cells | Gastric carcinoma | Homo sapiens | CVCL_1415 | ||
MKN45 cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0434 | ||
HGC-27 cells | Gastric carcinoma | Homo sapiens | CVCL_1279 | ||
NUGC-4 cells | Gastric signet ring cell adenocarcinoma | Homo sapiens | CVCL_3082 | ||
In Vivo Model |
The nude mice were raised in our laboratory for a week before the experiment. Then, 5 x 106 MKN-1 cells were subcutaneously injected to establish the subcutaneous xenograft tumour model in nude mice. When the maximum diameter of the xenograft tumours grew steadily to 1 cm, they were dissected completely and cut into 1 mm3 tissue fragments. Then, the tissue fragment was inserted into the surface of the serosa on the greater curvature of the stomach. Different doses of PB (2.5 mg/kg or 5.0 mg/kg) were given by intraperitoneal injection once a day for 3 weeks. The control group was given the same volume of vehicle. The positive control group was given 5-Fu at the dose of 10 mg/kg. The body weight and tumour size of nude mice were recorded. Mice were administered fluorescein substrate (150 mg/kg) intraperitoneally for in vivo imaging twice a week on a Xenogen IVIS 200 imaging system (Caliper Life Sciences, USA). The tumour inhibition rate was analysed using LT Living Image 4.3 Software.
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Response regulation | We identified a novel GPx4 inhibitor, polyphyllin B (PB), which can induce ferroptosis by down-regulating GPx4 expression in gastric cancer cells. It has also been shown to inhibit cell proliferation, suppress invasion and migration, induce apoptosis, and block the cell cycle progression in GC cellsin vitro. Then, immunofluorescence and western blotting assay confirmed that PB can regulate the expression of LC3B, TFR1, NOCA4 and FTH1 in vitro, which suggested that suggest that PB may increase the level of Fe2+by transporting Fe3+into the cell by TFR1 and promoting NCOA4-dependent iron autophagy. | ||||
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target | [17] | ||||
Target for Ferroptosis | Marker/Suppressor | ||||
Responsed Disease | Gastric cancer [ICD-11: 2B72] | ||||
Responsed Drug | Polyphyllin I | Investigative | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | MKN45 cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0434 | |
AGS cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0139 | ||
In Vivo Model |
A subcutaneous gastric tumor model was established by subcutaneously injecting 1 x 106 AGS cells or 2 x 106 MKN-45 cells near the right axilla of mice. Seven days after tumor cell inoculation, mice received daily i. p. Injection of PPI (3 mg/kg, dissolved in 1% DMSO + 5% PEG300 + 5% Tween 80 + 89% deionized water), as described previously, or the control solution with the same solvent. Mice were weighed at day 15, while tumor volumes were measured every 3 days and calculated using a formula: length x width2/2.
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Response regulation | For the first time, our results have demonstrated that Polyphyllin I exerts its antitumor activity on the gastric cancer by, at least partially, inducing cancer cell ferroptosisviaregulating NRF2/FTH1 pathway. | ||||
Fatty acid CoA ligase Acsl3 (ACSL3)
In total 1 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [10] | ||||
Target for Ferroptosis | Driver/Suppressor | ||||
Responsed Disease | Gastric cancer [ICD-11: 2B72] | ||||
Responsed Regulator | Perilipin-2 (PLIN2) | Suppressor | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Apoptosis | hsa04210 | ||||
Cell Process | Cell ferroptosis | ||||
Cell apoptosis | |||||
Cell proliferation | |||||
In Vitro Model | SGC-7901 cells | Gastric carcinoma | Homo sapiens | CVCL_0520 | |
MGC-803 cells | Gastric mucinous adenocarcinoma | Homo sapiens | CVCL_5334 | ||
In Vivo Model |
SGC7901 cell line transfected with OvPLIN2, ShPLIN2 and Control were injected subcutaneously into the nude mice (BALB/c nu/nu, female, 5 weeks old, Beijing Huafukang Biotechnology Co. Ltd. China) which were anaesthetized with 1% Sodium pentobarbital. The long diameter a and short diameter b of mouse tumor and the weights were measured every 4-5 days, and the relative tumor volumes (RTV) were calculated according to formula 0.5 x a x b x b.
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Response regulation | Overexpression and knockdown of PLIN2 augmented the proliferation and apoptosis of gastric carcinoma cell lines SGC7901 and MGC803, respectively. PLIN2 modulated Ferroptosis pathway through regulating transcription factors-PRDM11 and IPO7:ACSL3 was a critical gene involved in abnormal lipid metabolism, ALOX15 facilitated apoptosis and necrosis. | ||||
References