Open Access

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
  • View Affiliations

  • 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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December 2017
Volume 14 Issue 6

Print ISSN: 1792-1074
Online ISSN:1792-1082

2016 Impact Factor: 1.39
Ranked #68/217 Oncology
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APA
Dong, H., Huang, J., Zheng, K., Tan, D., Chang, Q., Gong, G. ... Zhang, S. (2017). Metformin enhances the chemosensitivity of hepatocarcinoma cells to cisplatin through AMPK pathway. Oncology Letters, 14, 7807-7812. https://doi.org/10.3892/ol.2017.7198
MLA
Dong, H., Huang, J., Zheng, K., Tan, D., Chang, Q., Gong, G., Zhang, Q., Tang, H., Sun, J., Zhang, S."Metformin enhances the chemosensitivity of hepatocarcinoma cells to cisplatin through AMPK pathway". Oncology Letters 14.6 (2017): 7807-7812.
Chicago
Dong, H., Huang, J., Zheng, K., Tan, D., Chang, Q., Gong, G., Zhang, Q., Tang, H., Sun, J., Zhang, S."Metformin enhances the chemosensitivity of hepatocarcinoma cells to cisplatin through AMPK pathway". Oncology Letters 14, no. 6 (2017): 7807-7812. https://doi.org/10.3892/ol.2017.7198