Could HBx protein expression affect signal pathway inhibition by Iressa or ARRY-142886?

Park YK, Kim KM, Lee YJ, Kim KH, Lee SG, Lee D, Shim JH, Lim YS, Lee HC, Chung YH, Lee YS, Suh DJ. "J Korean Med Sci. 2011 Feb"

Hepatitis B virus X (HBx) protein has long been known to perform an important part in development of hepatocellular carcinoma (HCC). The aim of this study would be to discover no matter whether HBx protein expression impacts antiproliferative impact of an epidermal growth aspect receptor-tyrosine kinase (EGFR-TK) inhibitor along with a MEK inhibitor in HepG2 and Huh-7 cell lines.

We set up HepG2 and Huh-7 cells transfected stably with HBx gene. HBx protein expression elevated pERK and pAkt expression together with β-catenin exercise in both cells. Iressa (EGFR-TK inhibitor) inhibited pERK and pAkt expression and β-catenin activity in both cells. ARRY-142886 (MEK inhibitor) decreased pERK degree and β-catenin activity but pAkt expression was relatively elevated by ARRY-142886 in these cells. Reduction of pERK ranges was significantly more powerful with ARRY-142886 than Iressa in both cells. The antiproliferative efficacy of ARRY-142886 was a lot more potent than that of Iressa.

However, the antiproliferative effect of Iressa, in addition to ARRY-142886, wasn't various among cell lines with or without HBx expression. Sign pathway activation by Hepatitis B virus X (HBx) might not be robust enough to attenuate the antiproliferative effect of EGFR-TK inhibitor.

Future experiments are necessary to understand the part of HBx protein expression in HCC treatment employing molecular focusing on agent.

Tags:

MEK inhibitor, Hepatitis-B-virus-X(HBx)