Metformin Inhibits Growth of Hepatocellular Carcinoma Cells by Inducing Apoptosis Via Mitochondrion-mediated Pathway

被引:39
|
作者
Xiong, Yu [1 ]
Lu, Qing-Jun [2 ]
Zhao, Jing [3 ]
Wu, Guo-Yang [1 ]
机构
[1] Xiamen Univ, Zhongshan Hosp, Dept Hepatoblliary Surg, Xiamen, Peoples R China
[2] Binzhou Cent Hosp, Dept Gen Surg, Binzhou, Peoples R China
[3] Shandong Univ, Prov Hosp, Dept Cardiac Surg Intens Care Unit, Jinan 250100, Peoples R China
关键词
Metformin; HCC; mTOR; apoptosis; signaling pathway; BREAST-CANCER; RISK; THERAPIES; KINASE; TRANSLATION; TARGET; COHORT;
D O I
10.7314/APJCP.2012.13.7.3275
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Recently, population-based studies of type 2 diabetes patients have provided evidence that metformin treatment is associated with a reduced cancer incidence and mortality, but its mode of action remains unclean Here we report effects of metformin on hepatocellular carcinoma (HCC) Hep-G2 cells and details of molecular mechanisms of metformin activity. Our research indicates that metformin displays anticancer activity against HCC through inhibition of the mTOR translational pathway in an AMPK-independent manner, leading to G1 arrest in the cell-cycle and subsequent cell apoptosis through the mitochondrion-dependent pathway. Furthermore, we showed that metformin strongly attenuated colony formation and dramatically inhibited Hep-G2 tumor growth in vivo. In conclusion, our studies suggested that metformin might have potential as a cytotoxic drug in the prevention and treatment of HCC.
引用
收藏
页码:3275 / 3279
页数:5
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