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目的:本试验通过检测三氧化二砷(As2O3)对前列腺癌(PCA)PC-3细胞周期素依赖性激酶(CDK)、CDK抑制剂(CDK I)pRb相关蛋白、E2F的影响,探讨其抗PCA的机制,为临床应用提供依据。方法:应用W esternb lotting及免疫沉淀技术检测细胞周期调节分子CDK、CDK I、周期素、pRb相关蛋白和E2F的变化及细胞周期素-CDK I和pRb相关蛋白-E2F复合物的形成;激酶试验测定As2O3对CDK、周期素相关激酶活性的影响。结果:As2O3可诱导PC-3细胞C ip1/p21和K ip1/p27呈计量依赖性增加,而CDK2,6和周期素E,A下调;As2O3增强周期素-CDK I的结合,而降低CDK2,4,6和周期素D1和E相关激酶的活性;As2O3使次磷酸化pRb/p107和pRb2/p130以及与E2F4结合增加。结论:As2O3以CDK I或Rb相关蛋白为作用靶点来阻止细胞周期进程、抑制细胞生长,具有治疗PCA的作用。
OBJECTIVE: To investigate the effect of arsenic trioxide (As2O3) on the expression of pRb-related protein and E2F in PC-3 cell cycle-dependent kinase (CDK), CDK inhibitor (CDK I) , Provide the basis for clinical application. Methods: The changes of cell cycle regulatory molecules such as CDK, CDK I, cyclin, pRb and E2F and the formation of cyclin-CDK I and pRb-associated protein-E2F were detected by Western blotting and immunoprecipitation. Kinase assay The effect of As2O3 on CDK and cyclin-related kinase activity was determined. RESULTS: As2O3 induced a dose-dependent increase of C ip1 / p21 and K ip1 / p27 in PC-3 cells, while down-regulation of CDK2,6 and cyclin E and A; As2O3 enhanced the binding of cyclin-CDK I and decreased CDK2, 4,6 and cyclin D1 and E-related kinase activity; As2O3 increased hypophosphorylated pRb / p107 and pRb2 / p130 and E2F4 binding. Conclusion: As2O3 targets CDK I or Rb-related proteins to prevent cell cycle progression, inhibit cell growth and has the potential to treat PCA.