Research Paper Volume 12, Issue 18 pp 18127—18136
GHR knockdown enhances the sensitivity of HCC cells to sorafenib
- 1 Department of Gastroenterology, The Third Affiliated Hospital of Naval Military Medical University, Shanghai 201800, China
- 2 Department of Gastroenterology, Zhongshan Qingpu Hospital Fudan University, Shanghai 201799, China
- 3 Department of Gastroenterology, Luoyang First People's Hospital, Luoyang 471000, China
- 4 Department of Traditional Chinese Medicine, Minhang Branch, Shanghai Cancer Center, Fudan University, Shanghai 200240, China
Received: March 25, 2019 Accepted: June 4, 2020 Published: September 24, 2020
https://doi.org/10.18632/aging.103625How to Cite
Copyright: © 2020 Gao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Sorafenib is approved for treatment of advanced hepatocellular carcinoma (HCC) by the Drug Administration. However, the efficacy of sorafenib has become very limited because most tumors have developed resistance to this drug. In this study, we found that sorafenib stimulated GHR expression in HCC cell lines. Thus, GHR might be linked to sorafenib resistance. To verify this hypothesis, we researched the roles of GHR knockdown and sorafenib combination in cell viability, apoptosis, cycle, and migration. The results showed that GHR blockage enhanced sorafenib blocking of cell cycle progression, leading to inhibition of this drug on HCC cell viability, and the improved promoting ability of sorafenib on cell apoptosis. In addition, it was found that GHR knockdown enhanced sorafenib inhibition of cell migration. The synergistic antitumor effects of sorafenib and GHR knockdown combination may be attributed to inhibition of PI3K/AKT/ERK1/2 signaling pathway. In conclusion, the findings suggest that GHR knockdown enhances the sensitivity of HCC cells to sorafenib. and the inactivation of PI3K/AKT/ERK1/2 signaling pathway may be the underlying mechanisms. This highlights the absence of GHR as a promising way to enhance sorafenib efficacy in HCC.