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背景与目的:许多研究表明,EGFR-STAT3信号传导通路参与肿瘤的形成。本试验目的在于探讨EG-FR-STAT3信号通路在大鼠实验性肝癌发生中的作用。方法:3’-甲基-4-二甲基偶氮苯(3’M e-DAB)诱发大鼠肝癌,免疫组化法检测EGFR、TGFα、STAT3、p-STAT3在诱癌各阶段的表达,分别用蛋白印记方法检测TGFα、STAT3、p-STAT3,原位杂交法检测STAT3在肝癌及正常肝组织中的表达,进行图像定量分析。结果:EGFR、TGFα、STAT3在肝细胞坏死和修复期表达有升高趋势。EGFR、TGFα、STAT3、p-STAT3在肝癌中100%表达,与正常组织比较,肝癌中EGFR、TGFα表达明显升高(P<0.05)。肝癌中STAT3在mRNA、蛋白水平的表达都较正常肝组织明显升高(P<0.05)。且其活化形式(p-STAT3)也显著增高(P<0.05)。肝癌中TGFα、p-STAT3表达具有相关性。结论:EG-FR-STAT3信号转导通路参与大鼠肝癌的发生,高表达的TGFα可激活EGFR信号转导通路形成自分泌环,并导致STAT3的持续活化。
BACKGROUND & AIM: Many studies have shown that EGFR-STAT3 signaling pathway is involved in the formation of tumors. The purpose of this study is to explore the role of EG-FR-STAT3 signaling pathway in the development of experimental liver cancer in rats. Methods: The rat liver cancer was induced by 3’-methyl-4-dimethylazobenzene (3’M e-DAB) and the expression of EGFR, TGFα, STAT3 and p-STAT3 was detected by immunohistochemistry The expressions of TGFα, STAT3 and p-STAT3 were detected by Western blotting and the expression of STAT3 in hepatocellular carcinoma (HCC) and normal liver tissues were detected by in situ hybridization. Quantitative image analysis was performed. Results: The expression of EGFR, TGFα, STAT3 in hepatocytes was increased during necrosis and repair. The expression of EGFR, TGFα, STAT3 and p-STAT3 in hepatocellular carcinoma was 100%. Compared with normal tissues, the expression of EGFR and TGFα in hepatocellular carcinoma was significantly increased (P <0.05). STAT3 mRNA and protein levels in hepatocellular carcinoma were significantly higher than those in normal liver tissue (P <0.05). And its activated form (p-STAT3) also significantly increased (P <0.05). There is a correlation between the expression of TGFα and p-STAT3 in hepatocellular carcinoma. CONCLUSION: The signal pathway of EG-FR-STAT3 is involved in the development of hepatocellular carcinoma in rats. High expression of TGFα can activate the EGFR signal transduction pathway to form an autocrine loop and lead to the sustained activation of STAT3.