丙型肝炎核心蛋白活化肝门部胆管癌细胞中NF-κB介导的信号转导途径

Hepatitis C virus core protein activates the NF-κB-dependent signal transduction pathway in hilar cholangiocarcinoma cells

目的 研究丙型肝炎核心蛋白 (HCVC蛋白 )致癌作用的细胞内信号转导途径(STPs)。方法 将构建成功的HCVC基因重组真核表达载体pcDNAHCV C ,分别与环AMP反应分子 (CRE)、血清反应因子 (SRF)、血清反应分子 (SRE)、活化蛋白 1(AP 1)及核转录因子 κB(NF κB)重组表达质粒共转染肝门部胆管癌细胞株 (QBC939) ,通过检测转染后细胞内荧光素酶活性确定与HCVC蛋白作用的信号转导分子。结果 HCVC蛋白通过NF κB介导的STPs ,使荧光素酶比活性较正常对照增高 7倍 ;而HCVC蛋白并不能激活QBC939细胞中与 pAP 1、pCRE、pSRF和pSRE相关信号转导途径。随着 pcDNAHCV C转染量的增多 ,NF κB被活化的程度也升高 ,两者呈剂量依存关系。结论 HCVC蛋白活化肝门部胆管癌细胞中NF κB介导的细胞内信号传导途径。

Objective To investigate whether hepatitis C virus (HCV) core protein has any effect on the intracellular signal transduction pathway which is supposed to be associated with cell proliferation,differentiation,and apoptosis.Methods pcDNAHCV-C and 5 viral protein-expression vectors of well-defined intracellular signaling pathways associated with cell proliferation,differentiation,and apoptosis were cotransfected and examined by using a reporter assay in QBC939 cells.The reporter vectors having a luciferase gene driven by the following inducible cis-enhancer elements of cyclic AMP response element (CRE),the serum response element (SRE),and the binding sites for NF-κB,activator protein 1 (AP-1),and serum response factor (SRF) were examined.Results HCV core protein activated the NF-κB-depondent signal transduction pathway.NF-κB expresion in QBC939 cells was increased in adose-dependent manner.Conclusion HCV core protein may play an important role in the pathogenesis of hilar cholangiocarcinogenesis through the activation of NF-κB-dependent signal transduction pathway.