苯乙双胍通过激活AMPK抑制肝癌细胞增殖、集落形成及侵袭  

Phenformin suppress liver cancer cell proliferation,colony formation and invasion by activating AMPK

作　　者：吴添雨 黄玲俐 颜新建 岳壮壮 伍燕 李高峰 WU Tianyu;HUANG Lingli;YAN Xinjian;YUE Zhuangzhuang;WU Yan;LI Gaofeng(Department of Oncology,Zhuzhou Hospital Affiliated to Xiangya School of Medicine,Central South University,Zhuzhou,Hunan 412000,China)

机构地区：[1]中南大学湘雅医学院附属株洲医院肿瘤科,湖南省株洲市412000

出　　处：《中南医学科学杂志》2021年第3期290-294,299,共6页Medical Science Journal of Central South China

基　　金：湖南省自然科学基金(2018JJ4097)。

摘　　要：目的探讨苯乙双胍对肝癌SMMC-7721、Hep-G2细胞系增殖、集落形成和侵袭的影响及分子机制。方法使用不同浓度苯乙双胍处理SMMC-7721细胞、Hep-G2细胞以及腺苷酸活化蛋白激酶(AMPK)沉默的Hep-G2细胞,MTT实验检测细胞增殖生长情况,克隆实验检测细胞集落形成能力,细胞侵袭实验检测细胞侵袭能力,蛋白印迹法(Western blot)检测AMPK和磷酸化哺乳动物雷帕霉素靶蛋白(mTOR)的表达。结果苯乙双胍抑制肝癌细胞增殖生长、集落形成以及侵袭能力。苯乙双胍处理组p-AMPK蛋白表达明显上升,p-mTOR蛋白表达明显下降,沉默AMPK后的Hep-G2细胞,苯乙双胍抑制肝癌细胞增殖和侵袭能力下降。结论苯乙双胍通过激活AMPK抑制肝癌细胞的增殖生长、集落形成和侵袭,为苯乙双胍应用于临床治疗肝癌提供理论基础。Aim To investigate the effects of phenformin on proliferation,colony formation and invasion of SMMC-7721 and Hep-G2 cells,and to explore the underlying molecular mechanism.Methods SMMC-7721,Hep-G2 and siAMPK cell lines were treated with different concentrations of phenformin.The proliferation of cells was detected by MTT assay,colony forming ability of cells was detected by clonal assay,invasion ability of cells was detected by Transwell assay,and the expression of phosphorylation of adenosine 5′-monophosphate(AMP)-activated protein kinase(AMPK),and phosphorylation mammalian target of rapamycin(mTOR)was detected by Western blot.Results Phenylformin inhibits the proliferation,growth,colony formation and invasion of hepatoma cells.After treatment with phenformin,the expression of p-AMPK protein was increased and the p-mTOR protein was decreased.Silencing AMPK of Hep-G2 cell,leads to the decline of proliferation and invasion by phenformin.Conclusion Phenformin inhibits the proliferation,colony formation and invasion of liver cancer cells by activating AMPK/mTOR pathway,and it is expected to be a drug for liver cancer.

关 键 词：苯乙双胍 肝癌细胞 AMPK 

分 类 号：R730.58[医药卫生—肿瘤]