Objective:To investigate the expression of Heat shock protein 72(Hsp72) in HCV infection and its role on the growth and proliferation of hepatocellular carcinoma cells with hepatitis C virus (HCV) infection.Methods: Sera and liver biopsy specimens from patients chronically infected with HCV were obtained for analysis of Hsp72 expression by ELISA, quantitative PCR and immunohistochemical staining.Hepatocytes upon infection with cell culture-grown HCV J6/JFH1 were used to investigate the role of over-expressed Hsp72 in proliferation of hepatocellular carcinoma cell with HCV infection by siRNA and cell proliferation assays.Results: Hsp72 expression was significantly upregulated in HCV infection.HCV increases Hsp72 expression level via induction of NFAT5.Hsp72 promotes proliferation of human hepatocellular carcinoma cells with HCV infection.The MAPK/MEK activation and cell proliferation driven by Hsp72 were suppressed by MEK inhibitor PD98095.Conclusions: The over-expressed of Hsp72 in HCV related HCC contributes to cell proliferation by activating MEK/Erk1/2.The role of Hsp72 and its importance for elimination of HCV in patients with HCC needs to take into account.%目的:评价感染丙型肝炎病毒(HCV)后热激蛋白72(Hsp72)的表达和其在肝癌细胞的增殖和生长过程中的作用.方法:选取感染基因型为1a/1b的HCV慢性肝炎患者32例,HBV和HCV检测为阳性患者20例,感染慢性肝炎病毒C的患者8例和未感染HBV、HCV或者HIV的肝转移瘤作为对照组肝3例,活组织检查样本来自感染慢性HCV的患者,通过ELISA、定量PCR和免疫组化的方法分析Hsp72的表达.运用培养感染HCV/JFH1的肝细胞,通过siRNA和细胞增值的方法来评价Hsp72过度表达对肝癌细胞增殖的作用.结果:①感染HCV后,细胞内的Hsp72蛋白表达显著上调.②HCV通过诱导NFAT5增加Hsp72的表达.③感染HCV后,Hsp72能促进人肝癌细胞的增殖.④MEK抑制剂PD98095可以抑制Hsp72对MAPK/MEK活化和细胞增殖.结论:Hsp72在HCV感染的HCC中过度表达通过激活MEK/ERk1/2而促进细胞增殖.应该重视Hsp72在治疗HCV感染的HCC患者中的作用及其重要性.
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