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Research Paper|Volume 12, Issue 23|pp 24255—24269

Exploring the mechanism of resistance to sorafenib in two hepatocellular carcinoma cell lines

Zhi Zhang1, Cheng-Zu He2, Ya-Qin Qin3, Jian-Jun Liao2, Shang-Tao Huang2, Steven Mo4, Hong-Mian Li5, Jian-Yan Lin6
  • 1Department of Hepatobiliary Surgery, The Fifth Affiliated Hospital of Guangxi Medical University, Nanning 530022, Guangxi, China
  • 2Department of Oncology, the People’s Hospital of Binyang County, Binyang 530405, Guangxi, China
  • 3Department of Liver Disease, The Affiliated Nanning Infectious Disease Hospital of Guangxi Medical University and The Fourth People’s Hospital of Nanning, Nanning 530023, Guangxi, China
  • 4YuanDong International Academy of Life Sciences, Nanning 530229, Guangxi, China
  • 5Department of Medical Laboratory Center, The Fifth Affiliated Hospital of Guangxi Medical University, Nanning 530022, Guangxi, China
  • 6Department of Public Health, The Affiliated Nanning Infectious Disease Hospital of Guangxi Medical University and The Fourth People’s Hospital of Nanning, Nanning 530023, Guangxi, China
* Equal contribution and co-first authors
Received: June 29, 2020Accepted: September 29, 2020Published: November 21, 2020
https://doi.org/10.18632/aging.104195

Copyright: © 2020 Zhang 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 has long been the only approved systemic therapy for advanced hepatocellular carcinoma (HCC), but most patients show primary or acquired drug resistance. In the present study, RNA was extracted from sorafenib-resistant and -sensitive clones of the HCC cell lines HepG2 and Huh7. Protein-protein interaction networks of the up- and down-regulated genes common to the two sorafenib-resistant cell lines were extracted and subjected to modular analysis in order to identify functional modules. Functional enrichment analysis showed the modules were involved in different biological processes and pathways. These results indicate that sorafenib resistance in HCC is complicated and heterogeneous. The potential regulators of each functional module, including transcription factors, microRNAs and long non-coding RNAs, were explored to construct a comprehensive transcriptional regulatory network related to sorafenib resistance in HCC. Our results provide new insights into sorafenib resistance of HCC at the level of transcriptional regulation.