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首页> 外文期刊>Journal of Korean medical science >Could HBx protein expression affect signal pathway inhibition by gefitinib or selumetinib, a MEK inhibitor, in hepatocellular carcinoma cell lines?
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Could HBx protein expression affect signal pathway inhibition by gefitinib or selumetinib, a MEK inhibitor, in hepatocellular carcinoma cell lines?

机译：HBx蛋白表达能否影响吉非替尼或selumetinib（MEK抑制剂）对肝癌细胞系的信号通路抑制作用？

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摘要

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.
机译：已知乙型肝炎病毒X（HBx）蛋白在肝细胞癌（HCC）的发生中起重要作用。这项研究的目的是找出HBx蛋白表达是否影响HepG2和Huh-7细胞系中的表皮生长因子受体酪氨酸激酶（EGFR-TK）抑制剂和MEK抑制剂的抗增殖作用。我们建立了稳定转染了HBx基因的HepG2和Huh-7细胞。 HBx蛋白表达在两个细胞中均增加了pERK和pAkt表达以及β-catenin活性。吉非替尼（EGFR-TK抑制剂）在两种细胞中均抑制pERK和pAkt表达以及β-catenin活性。 Selumetinib（MEK抑制剂）可降低pERK水平和β-catenin活性，但是在这些细胞中，selumetinib可以使pAkt表达明显升高。在两个细胞中，selumetinib的pERK水平降低均比gefitinib强得多。 selumetinib的抗增殖作用比gefitinib更为有效。但是，在有或没有HBx表达的细胞系中，吉非替尼和selumetinib的抗增殖作用没有差异。 HBx激活的信号途径可能不足以减弱EGFR-TK抑制剂的抗增殖作用。需要进一步的实验来了解HBx蛋白表达在使用分子靶向剂进行HCC治疗中的作用。

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