Related Experiment Video

Updated: Mar 6, 2026

An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis
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Overexpression of c-Jun contributes to sorafenib resistance in human hepatoma cell lines

Yuki Haga1, Tatsuo Kanda1, Masato Nakamura1

  • 1Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba, Japan.

Plos One
|March 22, 2017
PubMed
Abstract

Insights

Hepatocellular carcinoma (HCC) patients often resist sorafenib treatment. Targeting the c-Jun protein shows promise for overcoming this resistance and improving HCC therapy outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Hepatocellular carcinoma (HCC) remains difficult to cure despite advances in treatment.
  • Sorafenib, a multi-kinase inhibitor, is approved for advanced HCC but faces significant patient resistance.
  • Mechanisms underlying sorafenib resistance in HCC are not fully understood.

Purpose of the Study:

  • To investigate the role of molecules in the mitogen-activated protein kinase (MAPK) signaling pathway in sorafenib resistance.
  • To determine the involvement of Jun proto-oncogene (c-Jun) in sorafenib resistance in human hepatoma cells.

Main Methods:

  • Examined MAPK pathway molecule expression in human hepatoma cell lines with and without sorafenib.
  • Assessed apoptosis induction in sorafenib-treated hepatoma cells.
  • Measured the expression levels of c-Jun.

Main Results:

  • Sorafenib treatment enhanced the expression and phosphorylation of c-Jun in human hepatoma cell lines.
  • Inhibition of c-Jun increased sorafenib-induced apoptosis, while c-Jun overexpression reduced it.
  • Osteopontin, an AP-1 target gene, showed increased expression following sorafenib treatment.

Conclusions:

  • The protein c-Jun is implicated in sorafenib resistance in human hepatoma cell lines.
  • Modulating c-Jun expression and phosphorylation presents a potential therapeutic strategy to enhance sorafenib efficacy.
  • Targeting c-Jun may offer a new option for HCC patients resistant to sorafenib.

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