海南医科大学学报2025，Vol.31Issue(6)：415-420,6.DOI:10.13210/j.cnki.jhmu.20240823.001
二甲双胍通过AMPK/mTOR信号通路诱导胆囊癌细胞凋亡
Metformin increases apoptosis of human Gallbladder cancer cells through AMPK/mTOR signaling pathway
摘要
Abstract
Objective:To investigate the mechanism of metformin on the apoptosis and biological function of gallbladder can-cer cells through AMPK/mTOR signaling pathway.Methods:Gallbladder carcinoma cells were treated with different concentra-tions of metformin,and the inhibitory rate of metformin on NOZ cells was detected using the CCK-8 assay.The experiments were divided into three groups:blank control group,MET group and MET+BAY-3827 group.Colony formation assay was performed to detect the effect of metformin on the proliferation of NOZ cells.Western blot was used to detect the expressions of proteins linked to the AMPK/mTOR signaling pathway and proteins related to apoptosis,and flow cytometry was used to estimate the pro-portion of apoptotic cells.Wound healing assay and transwell assay were used to estimate cell migration efficiency.Results:Met-formin inhibited the proliferation and migration of gallbladder carcinoma cells and induced apoptosis via AMPK/mTOR signaling pathway.CCK-8 assay and colony formation assay showed that metformin could inhibit the proliferation of gallbladder carcinoma cells.Flow cytometry results indicated that metformin increased the ratio of apoptotic cells in gallbladder carcinoma cells,and the trend of metformin's effect on the expression of apoptosis-related proteins was reversed after inhibiting this signaling pathway with BAY-3827.Western blot results indicated that metformin upregulated the expression of apoptosis-related proteins Caspase-3 and Bax as well as AMPK and p-AMPK,and downregulated anti-apoptotic protein Bcl-2 and AMPK/mTOR signaling pathway-related proteins mTOR,p70S6K,4E-BP1,p-mTOR,p-p70S6K,and p-4E-BP1.Proliferation and migration of human gallbladder carcinoma were inhibited via metformin by activating the AMPK/mTOR signaling pathway,Besides,metformin upreg-ulated the expression of apoptosis-related proteins Caspase-3 and Bax and downregulated the expression of anti-apoptotic protein Bcl-2,thereby increased the proportion of apoptotic cells in normal gallbladder carcinoma cells.Conclusions:Metformin inhibits the proliferation and migration of gallbladder carcinoma cells and induces apoptosis by activating the AMPK/mTOR signaling path-way.关键词
胆囊癌/二甲双胍/信号通路/细胞凋亡Key words
Gallbladder carcinoma/Metformin/Signal pathway/Apoptosis分类
医药卫生引用本文复制引用
周汉旭,严华悦,王胜威,刘子祥,周少波..二甲双胍通过AMPK/mTOR信号通路诱导胆囊癌细胞凋亡[J].海南医科大学学报,2025,31(6):415-420,6.基金项目
This study was supported by Key Project of Natural Science Research in Higher Education Institutions in Anhui Province(2022AH051476) （2022AH051476）
Key Natural Science Project of Bengbu Medical College(2021byzd197) （2021byzd197）
Bengbu Medical College 2023 Graduate Research Innovation Plan(Byycx23110) 安徽省高等学校自然科学研究重点项目(2022AH051476) （Byycx23110）
蚌埠医学院自然科学重点项目(2021byzd197) （2021byzd197）
蚌埠医学院2023年度研究生科研创新计划(Byycx23110) （Byycx23110）
