Metformin enhances the chemosensitivity of hepatocarcinoma cells to cisplatin through AMPK pathway

Dong,Hao; Huang,Jungang; Zheng,Kang; Tan,Dong; Chang,Qi; Gong,Genqiang; Zhang,Qing; Tang,Hanqiu; Sun,Jianguo; Zhang,Shaoyu

doi:10.3892/ol.2017.7198

Metformin enhances the chemosensitivity of hepatocarcinoma cells to cisplatin through AMPK pathway

Authors:
- Hao Dong
- Jungang Huang
- Kang Zheng
- Dong Tan
- Qi Chang
- Genqiang Gong
- Qing Zhang
- Hanqiu Tang
- Jianguo Sun
- Shaoyu Zhang
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Affiliations: Department of Hepatobiliary Surgery, The Central Hospital of Xianyang, Xianyang, Shaanxi, P.R. China, Department of General Surgery, Traditional Chinese Medicine Hospital of Hanzhong, Hanzhong, Shaanxi, P.R. China, Department of General Surgery, 215 Hospital of Shaanxi Nuclear Industry, Xianyang, Shaanxi, P.R. China, Department of General Surgery, Affiliated Hospital of Yan'an University, Yan'an, Shaanxi, P.R. China, Department of General Surgery, The Central Hospital of Baoji, Baoji, Shaanxi, P.R. China, Department of Infectious Diseases, The Central Hospital of Hanzhong, Hanzhong, Shaanxi, P.R. China, Department of Hepatobiliary Surgery, The Central Hospital of Hanzhong, Hanzhong, Shaanxi, P.R. China, Xingyuan Hospital of Yulin City, Yulin, Shaanxi, P.R. China, Department of Gastroenterology, Traditional Chinese Medicine Hospital of Baoji, Baoji, Shaanxi, P.R. China
Published online on: October 17, 2017 https://doi.org/10.3892/ol.2017.7198
Pages: 7807-7812
Copyright: © Dong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

This study investigated the effect of metformin on chemosensitivity of hepatocarcinoma cells to cisplatin and the possible mechanism. HepG2 and Huh-7 hepatoma cells were treated with cisplatin at concentrations of 0, 2, 4, 6, 8 and 10 µM for 48 h. Proliferation of HepG2 and Huh-7 hepatoma cells were detected by MTT assay. Apoptosis of hepatocellular carcinoma cells was detected by flow cytometry. Western blot analysis was used to detect the expression of 5-monophosphate-activated protein kinase (AMPK) and p-AMPK protein. Proliferative activity of HepG2 and Huh-7 cells decreased with the increase of cisplatin concentration. After adding metformin, proliferation ability of hepatocarcinoma cells was significantly reduced. Apoptosis rate of the metformin was significantly higher than that of the control group, and apoptosis rate of the cisplatin + metformin was significantly higher than that of the cisplatin group. There was no significant difference in expression level of AMPK protein found between control, metformin, cisplatin and cisplatin + metformin group. Compared with the control, ratio of p-AMPK/AMPK in metformin group was increased, and ratio of p-AMPK/AMPK in cisplatin + metformin was significantly higher than that in cisplatin group. Activity of cells in cisplatin + metformin + compound C (AMPK pathway blocker) group was significantly higher than that of cisplatin + metformin, while apoptosis of cells in cisplatin + metformin + compound C (AMPK pathway blocker) was significantly lower than that of cisplatin + metformin group. In conclusion, metformin can inhibit the proliferation, promote apoptosis and enhance the chemosensitivity of hepatocarcinoma cells to cisplatin through AMPK pathway.

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