Could HBx protein expression affect signal pathway inhibition by gefitinib or selumetinib, a MEK inhibitor, in hepatocellular carcinoma cell lines?

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 β-catenin activity in both cells. Gefitinib (EGFR-TK inhibitor) inhibited pERK and pAkt expression and β-catenin activity in both cells. Selumetinib (MEK inhibitor) reduced pERK level and β-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.

• Authors: Yoon Kyung Park, 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
• Journal: Journal of Korean medical science (J Korean Med Sci) Vol. 26 Issue 2 Pg. 214-21 (Feb 2011) ISSN: 1598-6357 [Electronic] Korea (South)
• PMID: 21286012 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• AZD 6244
• Antineoplastic Agents
• Benzimidazoles
• Protein Kinase Inhibitors
• Quinazolines
• Trans-Activators
• Viral Regulatory and Accessory Proteins
• beta Catenin
• hepatitis B virus X protein
• ErbB Receptors
• Proto-Oncogene Proteins c-akt
• Extracellular Signal-Regulated MAP Kinases
• Mitogen-Activated Protein Kinase Kinases
• Gefitinib

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Benzimidazoles (pharmacology)
• Carcinoma, Hepatocellular (metabolism)
• Cell Line, Tumor (drug effects)
• Cell Proliferation
• ErbB Receptors (antagonists & inhibitors)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Gefitinib
• Humans
• Liver Neoplasms (metabolism)
• Mitogen-Activated Protein Kinase Kinases (antagonists & inhibitors)
• Protein Kinase Inhibitors (pharmacology)
• Proto-Oncogene Proteins c-akt
• Quinazolines (pharmacology)
• Signal Transduction (drug effects)
• Trans-Activators (metabolism)
• Viral Regulatory and Accessory Proteins
• beta Catenin (metabolism)