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Metformin promotes ferroptosis and sensitivity to sorafenib in hepatocellular carcinoma cells via ATF4/STAT3 期刊论文

编号：

C8DFBEDDFE0BEBE393EF63860E60660B
作者：

Hu, Zongqiang(胡宗强)#^[1,2]Zhao, Yingpeng(赵英鹏)^[1,2]Li, Laibang^[1,2];Jiang, Jie^[1,2];Li, Wang^[1,2];Mang, Yuanyi^[1,2];Gao, Yang^[1,2];Dong, Yun^[1,2];Zhu, Jiashun^[1,2];Yang, Chaomin^[1,2];Ran, Jianghua(冉江华)*^[1,2]Li, Li(李立)*^[1,2]Zhang, Shengning(张升宁)*^[1,2]
语种：

英文
期刊：

MOLECULAR BIOLOGY REPORTS ISSN：0301-4851 2023 年 50 卷 8 期 (6399 - 6413) ; AUG
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关键词：

Hepatocellular carcinoma Metformin Sorafenib resistance Ferroptosis ATF4 STAT3
摘要：

BackgroundHepatocellular carcinoma (HCC) is a common cancer worldwide, and sorafenib is a first-line drug for the treatment of advanced liver cancer. Resistance to sorafenib has become a major challenge in the treatment of hepatocellular carcinoma, however, studies have shown that metformin can promote ferroptosis and sorafenib sensitivity. Therefore, the aim of this study was to investigate the promotion of ferroptosis and sorafenib sensitivity by metformin via ATF4/STAT3 in hepatocellular carcinoma cells.MethodsHepatocellular carcinoma cells Huh7 and Hep3B and induced sorafenib resistance (SR) Huh7/SR and Hep3B/SR cells were used as in vitro cell models. Cells were injected subcutaneously to establish a drug-resistant mouse model. CCK-8 was used to detect cell viability and sorafenib IC50. Western blotting was used to detect the expression of relevant proteins. BODIPY staining was used to analyze the lipid peroxidation level in cells. A scratch assay was used to detect cell migration. Transwell assays were used to detect cell invasion. Immunofluorescence was used to localize the expression of ATF4 and STAT3.ResultsMetformin promoted ferroptosis in hepatocellular carcinoma cells through ATF4/STAT3, decreased sorafenib IC50, increased ROS and lipid peroxidation levels, decreased cell migration and invasion, inhibited the expression of the drug-resistant proteins ABCG2 and P-GP in hepatocellular carcinoma cells, and thus inhibited sorafenib resistance in hepatocellular carcinoma cells. Downregulating ATF4 inhibited the phosphorylated nuclear translocation of STAT3, promoted ferroptosis, and increased the sensitivity of Huh7 cells to sorafenib. Metformin was also shown in animal models to promote ferroptosis and sorafenib sensitivity in vivo via ATF4/STAT3.ConclusionMetformin promotes ferroptosis and sensitivity to sorafenib in hepatocellular carcinoma cells via ATF4/STAT3, and it inhibits HCC progression.
推荐引用方式
GB/T 7714：

Hu Zongqiang,Zhao Yingpeng,Li Laibang, et al. Metformin promotes ferroptosis and sensitivity to sorafenib in hepatocellular carcinoma cells via ATF4/STAT3 [J].MOLECULAR BIOLOGY REPORTS,2023,50(8):6399-6413.
APA：

Hu Zongqiang,Zhao Yingpeng,Li Laibang,Jiang Jie,&Zhang Shengning.(2023).Metformin promotes ferroptosis and sensitivity to sorafenib in hepatocellular carcinoma cells via ATF4/STAT3 .MOLECULAR BIOLOGY REPORTS,50(8):6399-6413.
MLA：

Hu Zongqiang, et al. "Metformin promotes ferroptosis and sensitivity to sorafenib in hepatocellular carcinoma cells via ATF4/STAT3" .MOLECULAR BIOLOGY REPORTS 50,8(2023):6399-6413.
入库时间：

2023/7/15 21:52:53
更新时间：

2023/7/15 21:52:53
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