Combination of metformin and sorafenib suppresses proliferation and induces autophagy of hepatocellular carcinoma via targeting the mTOR pathway

  • Authors:
    • Sunbin Ling
    • Lei Song
    • Ning Fan
    • Tingting Feng
    • Lu Liu
    • Xu Yang
    • Mingjie Wang
    • Yanling Li
    • Yu Tian
    • Feng Zhao
    • Ying Liu
    • Qihong Huang
    • Zhaoyuan Hou
    • Fei Xu
    • Lei Shi
    • Yan Li
  • View Affiliations

  • Published online on: December 9, 2016     https://doi.org/10.3892/ijo.2016.3799
  • Pages: 297-309
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Abstract

The multi‑kinase inhibitor sorafenib is the only drug for which randomized control trials have shown improved patient survival in advanced hepatocellular carcinoma (HCC). However, life expectancy is extended in these cases by only a few months. The anti‑type II diabetes agent metformin was used in this study in an effort to find a more efficient approach to HCC treatment. Sorafenib effectively reversed the activation status of mTORC2 induced by metformin and enhanced the suppression of the mTORC1 and MAPK pathway by metformin in HCC cells, which may be responsible for reduced proliferation upon combined treatment. The metformin and sorafenib combination led to increased impaired proliferation and tumor inhibition of HCC in vitro and in vivo compared to single agent, which was partially bridged by disrupting the mTORC1/mTORC2 feedback loop. Metformin and sorafenib cooperated to promote apoptosis and autophagy in HCC cells. Pharmacological inhibition of autophagy sensitized HCC cells to metformin and sorefenib‑induced apoptotic cell death. Therefore, the anti‑autophagy treatment should be considered in metformin and sorafenib-based treatments in HCC cells.
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January-2017
Volume 50 Issue 1

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Spandidos Publications style
Ling S, Song L, Fan N, Feng T, Liu L, Yang X, Wang M, Li Y, Tian Y, Zhao F, Zhao F, et al: Combination of metformin and sorafenib suppresses proliferation and induces autophagy of hepatocellular carcinoma via targeting the mTOR pathway. Int J Oncol 50: 297-309, 2017
APA
Ling, S., Song, L., Fan, N., Feng, T., Liu, L., Yang, X. ... Li, Y. (2017). Combination of metformin and sorafenib suppresses proliferation and induces autophagy of hepatocellular carcinoma via targeting the mTOR pathway. International Journal of Oncology, 50, 297-309. https://doi.org/10.3892/ijo.2016.3799
MLA
Ling, S., Song, L., Fan, N., Feng, T., Liu, L., Yang, X., Wang, M., Li, Y., Tian, Y., Zhao, F., Liu, Y., Huang, Q., Hou, Z., Xu, F., Shi, L., Li, Y."Combination of metformin and sorafenib suppresses proliferation and induces autophagy of hepatocellular carcinoma via targeting the mTOR pathway". International Journal of Oncology 50.1 (2017): 297-309.
Chicago
Ling, S., Song, L., Fan, N., Feng, T., Liu, L., Yang, X., Wang, M., Li, Y., Tian, Y., Zhao, F., Liu, Y., Huang, Q., Hou, Z., Xu, F., Shi, L., Li, Y."Combination of metformin and sorafenib suppresses proliferation and induces autophagy of hepatocellular carcinoma via targeting the mTOR pathway". International Journal of Oncology 50, no. 1 (2017): 297-309. https://doi.org/10.3892/ijo.2016.3799