Could HBx Protein Expression Affect Signal Pathway Inhibition by Gefitinib or Selumetinib, a MEK Inhibitor, in Hepatocellular Carcinoma Cell Lines?.
10.3346/jkms.2011.26.2.214
- Author:
Yoon Kyung PARK
1
;
Kang Mo KIM
;
Young Joo LEE
;
Ki Hun KIM
;
Sung Gyu LEE
;
Danbi LEE
;
Ju Hyun SHIM
;
Young Suk LIM
;
Han Chu LEE
;
Young Hwa CHUNG
;
Yung Sang LEE
;
Dong Jin SUH
Author Information
1. Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. kimkm70@amc.seoul.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Hepatocellular Carcinoma;
HBx protein;
Gefitinib;
Selumetinib;
EGFR;
MEK
- MeSH:
Animals;
Antineoplastic Agents/*pharmacology;
Benzimidazoles/*pharmacology;
Carcinoma, Hepatocellular/*metabolism;
Cell Line, Tumor/drug effects;
Cell Proliferation;
Extracellular Signal-Regulated MAP Kinases/metabolism;
Humans;
Liver Neoplasms/*metabolism;
Mitogen-Activated Protein Kinase Kinases/*antagonists & inhibitors;
Protein Kinase Inhibitors/*pharmacology;
Proto-Oncogene Proteins c-akt;
Quinazolines/*pharmacology;
Receptor, Epidermal Growth Factor/antagonists & inhibitors;
Signal Transduction/*drug effects;
Trans-Activators/*metabolism;
beta Catenin/metabolism
- From:Journal of Korean Medical Science
2011;26(2):214-221
- CountryRepublic of Korea
- Language:English
-
Abstract:
Hepatitis B virus X (HBx) protein has been known to play an important role in development of hepatocellular carcinoma (HCC). The aim of this study is to find out whether HBx protein expression affects antiproliferative effect of an epidermal growth factor receptor-tyrosine kinase (EGFR-TK) inhibitor and a MEK inhibitor in HepG2 and Huh-7 cell lines. We established HepG2 and Huh-7 cells transfected stably with HBx gene. HBx protein expression increased pERK and pAkt expression as well as beta-catenin activity in both cells. Gefitinib (EGFR-TK inhibitor) inhibited pERK and pAkt expression and beta-catenin activity in both cells. Selumetinib (MEK inhibitor) reduced pERK level and beta-catenin activity but pAkt expression was rather elevated by selumetinib in these cells. Reduction of pERK levels was much stronger with selumetinib than gefitinib in both cells. The antiproliferative efficacy of selumetinib was more potent than that of gefitinib. However, the antiproliferative effect of gefitinib, as well as selumetinib, was not different between cell lines with or without HBx expression. Signal pathway activation by HBx might not be strong enough to attenuate the antiproliferative effect of EGFR-TK inhibitor. Future experiments are needed to understand the role of HBx protein expression in HCC treatment using molecular targeting agent.
