三氧化二砷对前列腺癌PC-3细胞周期调节分子的影响

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（CDKI）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Western blotting及免疫沉淀技术检测细胞周期调节分子CDK、CDKI、周期素、pRb相关蛋白和E2F的变化及细胞周期素-CDKI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Cip1／p21和Kip1／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-CDKI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CDKI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。

The anti-cancer effects of arsenic trioxide in prostate carcinoma PC-3 cells

Objective:To investigate the modulation of CDKI-CDK-cyclin and pRb-related protein-E2F complexes of arsenic trioxide(As_(2)O_(3)) in human prostate carcinoma(PCA) PC-3 cells,offering experimental evidences for clinical application of As_(2)O_(3) in PCA.Methods:Western immunoblotting,immunoprecipitation and kinase assay were performed to investigate the involvement of G1 regulators and their interplay.Results:As_(2)O_(3)strongly increased the expression of CDKI(cyclin-dependent kinase inhibitors),Cip1/p21 and Kip1/p27,as well as down-regulate CDK2,6 and cyclinE,A.As_(2)O_(3) inhibited kinase activities associated with CDK2,4 and 6,and cyclin E and D1.Further studies showed the increased binding of Kip/p27 and Cip1/p21 with cyclin D1 and E.In down-stream of CDKI-CDK/cyclin cascade, As_(2)O_(3) increased hypophosphorylated levels of Rb-related proteins and an increased sequestration of E2F4.Conclusion:As_(2)O_(3) could halt cell cycle progression by targeting CDKI or Rb-related proteins,so can be developed as a new anti-cancer agent against PCA.