小檗碱增强表柔比星诱导T24细胞G_0/G_1期阻滞的作用机制

目的:探讨小檗碱联合表柔比星对膀胱癌T24细胞周期的影响及相关作用机制。方法:实验将膀胱癌T24细胞分为4组:对照组、表柔比星组、表柔比星+小檗碱组和小檗碱组,采用MTT法检测细胞的活力,检测药物处理后对膀胱癌T24细胞增殖的抑制情况。用流式细胞术分析T24细胞周期分布并用Western blot法测定cyclin D1、CDK2、CDK4、P21和P27蛋白的表达水平。结果:小檗碱联合表柔比星显著抑制T24细胞的活力,存在时间依赖性,联合用药组的G_0/G_1期细胞比例增高,S期和G_2期细胞比例降低,与单用药物组及对照组比较有显著性差异(P0.05)。联合用药上调细胞周期依赖性激酶抑制蛋白P27和P21蛋白的表达水平,同时下调cyclin D1、CDK2及CDK4细胞周期蛋白的表达水平。结论:小檗碱增强表柔比星对膀胱癌T24细胞增殖的抑制及G_0/G_1期阻滞,其作用机制可能与上调P27及P21蛋白和抑制cyclin D1、CDK2及CDK4蛋白表达有关。

Berberine promotes epirubicin-induced G0/G1 phase arrest in T24 bladder cancer cells

AIM: To observe the effects of the combination of berberin and epirubicin on the cell cycle of T24 bladder cancer cells and the underlying mechanisms.METHODS: The cancer cells were exposed to epirubicin in the presence or absence of different concentrations of berberin. The viability of the cancer cells was determined by MTT assay. The cell cycle distribution was detected by flow cytometry, and the protein levels of cyclin D1, CDK2, CDK4, P21 and P27 were detected by Western blot.RESULTS: Berberine markedly enhanced the inhibitory effect of epirubicin on the viability of T24 cells and promoted epirubicin-induced cell cycle arrest at G₀/G₁ phase as compared with the negative control cells. Epirubicin increased the protein expression of P27 and P21, both of which were enhanced by treatment with berberin. In contrast, berberin exposure further decreased the protein expression of cyclin D1, CDK2 and CDK4 in epirubicin-treated T24 cells.CONCLUSION: Berberine significantly promotes epirubicin-induced G₀/G₁ phase arrest in human bladder cancer cells by up-regulating P27 and P21 expression and inhibiting the expression of cyclin D1, CDK2 and CDK4.