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[目的]探讨EGFR-STAT3信号转导通路在大鼠实验性肝内胆管细胞癌形成过程中的表达及活化。[方法]3′-甲基-4-二甲基偶氮苯(3′Me-DAB)诱发大鼠肝癌,免疫组化法检测EGFR、TGFα、STAT3、p-STAT3在胆管细胞癌中的表达,原位杂交法检测STAT3在胆管细胞癌及正常肝组织中mRNA的表达,KS400图象分析系统进行图象半定量分析。[结果]EGFR、TGFα、STAT3、p-STAT3在胆管细胞癌中100%表达,与正常组织相比,胆管细胞癌中EGFR、TGFα表达明显升高(P<0.05)。胆管细胞癌中STAT3在mRNA、蛋白水平的表达较正常胆管及增生胆管中明显升高(P<0.05),p-STAT3也显著增高(P<0.05)。胆管细胞癌中p-STAT3与TGFα的表达呈正相关性(P<0.05)。[结论]胆管细胞癌中STAT3在转录、蛋白表达及活化水平显著增强,STAT3在胆管细胞癌中的持续活化与上游信号转导通路EGFR-TGFα自分泌环作用增强有关。
[Objective] To investigate the expression and activation of EGFR-STAT3 signal transduction pathway in the process of experimental intrahepatic cholangiocarcinoma in rats. [Method] The rat liver cancer was induced by 3’-methyl-4-dimethylazobenzene (3’Me-DAB) and the expression of EGFR, TGFα, STAT3 and p-STAT3 in cholangiocarcinoma was detected by immunohistochemistry , In situ hybridization STAT3 mRNA expression in cholangiocarcinoma and normal liver tissue, KS400 image analysis system for semi-quantitative image analysis. [Results] The expression of EGFR, TGFα, STAT3 and p-STAT3 in cholangiocarcinoma was 100%. Compared with normal tissues, the expression of EGFR and TGFα in cholangiocarcinoma was significantly increased (P <0.05). The expression of STAT3 mRNA and protein in cholangiocarcinoma was significantly higher than that in normal bile duct and hyperplastic duct (P <0.05), and p-STAT3 was also significantly increased (P <0.05). The expression of p-STAT3 and TGFα in cholangiocarcinoma was positively correlated (P <0.05). [Conclusion] STAT3 in cholangiocarcinoma is significantly increased in transcription, protein expression and activation, and the sustained activation of STAT3 in cholangiocarcinoma is related to the enhancement of the autocrine loop of EGFR-TGFα in the upstream signal transduction pathway.