索拉非尼对人肝癌细胞的体外杀伤作用与磷酸化胞外信号调节激酶基础表达水平的关系

The relationship between effects of sorafenib on cell proliferation and basal phosphorylated extra- cellular signal-regulated kinase levels in different HCC cell lines

目的探讨索拉非尼对不同肝细胞肝癌（HCC）细胞株的体外杀伤作用与基础磷酸化胞外信号调节激酶（pERK）表达水平的关系。方法应用细胞免疫化学定量分析和Western blot方法检测方法，评价不同浓度（0．01～30．00μmol／L）索拉非尼对4种人肝癌细胞（SMMC-7721、MHCC97-L、MHCC97-H和HCCLM6）体外杀伤作用与细胞基础pERK表达的相关性。结果4种细胞株基础pERK蛋白表达含量随着转移潜能依次递增。索拉非尼对各细胞株的IC50与pERK蛋白表达呈负相关（Spearmanr=-0．8671，P〈0．01，n=12），提示索拉非尼的药物敏感性与细胞基础pERK蛋白水平存在显著的相关性。结论pERK可以作为一个潜在的生物标记物，预测索拉非尼对肝细胞癌的药物敏感性。

Objective To investigate the relationship between effects of sorafenib on cell proliferation and basal phosphorylated extracellular signal-regulated kinase （pERK） levels in different HCC cell lines. Methods pERK expression was quantitatively detected by immunocytochemistry and Western blot. The effects of various concentrations of sorafenib （0.01-30.00 μmol/L） on cell proliferation were evaluated by cell viability assay in four types of HCC cell line （SMMC-7721, MHCC97-L, MHCC97-H and HC- CLM6）. Correlation analysis was carried out between the IC50 values of drugs and mean absorbance （A） values of pERK. Results The basal pERK levels were increased stepwise in cell lines in accordance with their metastatic potential. Correlation analysis between the IC50 values and mean A values of pERK revealed that the effects of sorafenib were significantly correlated with basal pERK levels （ Spearman r = - 0.8671, P 〈 0.01 ）. Conclusion pERK was confirmed to be a useful biomarker predictive of sensitivity in treating HCC with sorafenib.