Open Access

Sorafenib prevents the proliferation and induces the apoptosis of liver cancer cells by regulating autophagy and hypoxia-inducible factor-1

  • Authors:
    • Qingzhuang Yang
    • Lianghui Gao
    • Xiaolong Huang
    • Jie Weng
    • Youke Chen
    • Shibu Lin
    • Qiushi Yin
  • View Affiliations

  • Published online on: July 12, 2021     https://doi.org/10.3892/etm.2021.10412
  • Article Number: 980
  • Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Sorafenib has been approved as a systemic drug for advanced liver cancer; however, the underlying mechanisms remain unclear. The present study aimed to investigate the effects of sorafenib on the proliferation, autophagy and apoptosis of HepG2 cells under hypoxia. Briefly, reverse transcription-quantitative PCR and western blotting was performed to quantify HIF-1, LC3II/I, mTOR and p70s6K expression levels. Cell proliferation was determined using the Cell Counting Kit‑8 assay and the cell apoptosis rate was evaluated using flow cytometry. The results demonstrated that autophagy and apoptosis were induced by hypoxia, and that sorafenib further enhanced hypoxia-induced autophagy and apoptosis in HepG2 cells in a dose-dependent manner. Furthermore, the mechanism of sorafenib-mediated autophagy in liver cancer cell were investigated by using chloroquine (CQ). The results showed that CQ significantly inhibited autophagy by decreasing LC3II/LC3I ratio in HepG2 cells treated with sorafenib and/or hypoxia. By contrast, sorafenib could increase the expression of hypoxia-inducible factor-1 (HIF-1) and of the autophagy marker (LC3II/I) and decrease the expression of mammalian target of rapamycin and p70 ribosomal S6 kinase in HepG2 cells under normoxia and hypoxia conditions, suggesting that sorafenib could induce hypoxia and autophagy in liver cancer cells. In addition, sorafenib was demonstrated to prevent proliferation and induce apoptosis of HepG2 cells under normoxia and hypoxia. Sorafenib could also prevent the malignant behavior of HepG2 by inducing hypoxia and autophagy. In summary, the findings from the present study suggested that sorafenib may inhibit liver cancer progression by activating autophagy and HIF-1 signaling pathway.

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September-2021
Volume 22 Issue 3

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Yang Q, Gao L, Huang X, Weng J, Chen Y, Lin S and Yin Q: Sorafenib prevents the proliferation and induces the apoptosis of liver cancer cells by regulating autophagy and hypoxia-inducible factor-1. Exp Ther Med 22: 980, 2021
APA
Yang, Q., Gao, L., Huang, X., Weng, J., Chen, Y., Lin, S., & Yin, Q. (2021). Sorafenib prevents the proliferation and induces the apoptosis of liver cancer cells by regulating autophagy and hypoxia-inducible factor-1. Experimental and Therapeutic Medicine, 22, 980. https://doi.org/10.3892/etm.2021.10412
MLA
Yang, Q., Gao, L., Huang, X., Weng, J., Chen, Y., Lin, S., Yin, Q."Sorafenib prevents the proliferation and induces the apoptosis of liver cancer cells by regulating autophagy and hypoxia-inducible factor-1". Experimental and Therapeutic Medicine 22.3 (2021): 980.
Chicago
Yang, Q., Gao, L., Huang, X., Weng, J., Chen, Y., Lin, S., Yin, Q."Sorafenib prevents the proliferation and induces the apoptosis of liver cancer cells by regulating autophagy and hypoxia-inducible factor-1". Experimental and Therapeutic Medicine 22, no. 3 (2021): 980. https://doi.org/10.3892/etm.2021.10412