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目的通过检测葡萄糖调节蛋白78(Grp78)、细胞外信号调节激酶(ERK1/2)、磷酸化ERK1/2在肝细胞癌手术切除组织中的表达,并在SMMC-7721细胞中干预Grp78的表达,探讨Grp78对ERK1/2激酶的调控作用。方法应用免疫组织化学方法(IHC)和免疫印迹法检测47例肝细胞癌手术切除组织样本中Grp78,ERK1/2的表达和ERK1/2磷酸化水平;在高表达Grp78的肝细胞癌细胞系SMMC-7721中,通过用小RNA干扰Grp78的表达来探讨Grp78表达水平,改变对ERK1/2活性及表达的影响。结果在肝细胞癌组织样本中,Grp78的表达情况与ERK1/2和磷酸化ERK1/2的表达明显呈正相关。在SMMC-7721细胞中Grp78高表达促进ERK1/2的磷酸化,应用RNA干扰特异性下调Grp78高表达细胞中Grp78水平可以抑制ERK1/2的磷酸化。结论Grp78参与调解ERK1/2信号通路,并且在肝细胞癌临床治疗方面可能成为潜在的治疗靶点。
Objective To detect the expression of Grp78, ERK1 / 2 and ERK1 / 2 in hepatocellular carcinoma (HCC) tissues and to investigate the expression of Grp78 in SMMC-7721 cells. To investigate the regulation of Grp78 on ERK1 / 2 kinase. Methods The expressions of ERK1 / 2 and Grp78, ERK1 / 2 were detected by immunohistochemistry (IHC) and Western blotting in 47 cases of hepatocellular carcinoma. In the hepatocellular carcinoma cell line SMMC -7721 by Grp78 expression of small RNA interference to explore Grp78 expression level, change the activity and expression of ERK1 / 2 impact. Results The expression of Grp78 in hepatocellular carcinoma tissue was positively correlated with the expression of ERK1 / 2 and phosphorylated ERK1 / 2. Grp78 overexpression promotes the phosphorylation of ERK1 / 2 in SMMC-7721 cells. The down-regulation of Grp78 in Grp78-overexpressing cells by RNA interference can inhibit the phosphorylation of ERK1 / 2. Conclusion Grp78 is involved in mediating the ERK1 / 2 signaling pathway and may be a potential therapeutic target in the clinical treatment of hepatocellular carcinoma.