信号转导和转录激活因子3持续活化通路蛋白参与二乙基亚硝胺诱发大鼠肝癌发生研究

Sustained activation pathway of signal transducers and activators of transcription factor 3 protein involved in DEN-induced rat hepatocarcinogenesis

[目的]探讨信号转导和转录激活因子3(STAT-3)信号转导通路在二乙基亚硝胺(DEN)诱发大鼠肝癌发生、发展过程表达的意义.[方法]采用二乙基亚硝胺(DEN)间断给药诱发大鼠肝癌模型,利用光学显微镜技术观察诱癌过程中肝组织的形态学变化;采用Western blotting技术检测STAT-3,p-STAT-3及人基质金属蛋白酶10(MMP-10)、血管内皮生长因子(VEGF)、激酶功能区受体(KDR)、缺氧诱导因子(HIF)-1α,碱性成纤维生长因子(bFGF)和白细胞介素10(IL-10)的表达水平,并探讨其相关性.[结果]DEN诱发大鼠肝癌发生过程中,STAT-3蛋白持续活化MMP-10,VEGF,KDR,HIF-1α,bFGF和IL-10,并且与这些蛋白的表达呈正相关.[结论]DEN诱发大鼠肝癌中,STAT-3持续活化MMP-10,VEGF,KDR,HIF-1α,bFGF和IL-10参与其过程.

OBJECTIVE To study the expression of sustained activation pathway of signal transducers and activators of transcription factor 3 （STAT-3） protein in diethylnitrosamine （DEN）-induced rat hepatocarcinogenesis. METHODS The rat models of liver cancer were established by intermittently administration with the DEN and the morphological changes in hepatocarcinogenesis were observed by light microscope. It was detected by Western blotting and studied their correlation that the expression of STAT-3, p-STAT-3, matrix metalloproteinases-10 （MMP-10）, vascular endothelial growth factor （VEGF）, kinase insert domain-containing receptor （KDR）, hypoxia-inducible factor-1a （HIF-1a）, basic fibroblast growth factor （bFGF） and interleukin 10 （IL-10）. RESULTS The STAT-3 protein activated continually the MMP-10, VEGF, KDR, HIF-la, bFGF and IL-10 in the process of DEN-induced rat hepatocarcinogenesis, and had positive correlation with the expression of above proteins. CONCLUSION STAT-3 protein activates continually the MMP-10, VEGF, KDR, HIF-1a, bFGF and IL-10, and participates in process of DEN- induced rat hepatocarcinogenesis.