Berberine enhances mitomycin C-induced cell cycle arrest and apoptosis of T24 bladder cancer cells / 中国病理生理杂志

ABSTRACT

AIM:To observe the effects of the combination of berberin (Ber) and mitomycin C (MMC) on the cell cycle arrest and apoptosis of T24 bladder cancer cells and the underlying mechanisms. METHODS:The T24 cells were exposed to MMC in the presence or absence of difference concentrations of Ber. The viability of the T24 cells was de-termined by CCK-8 assay. The cell cycle distribution was detected by flow cytometry. The apoptosis was analyzed by flow cytometry with Annexin V-FITC/PI staining, and the protein expression levels of cyclin D1, survivin, CDK2, CDK4, p21 and p27 were determined by Western blot. RESULTS:CCK-8 experiments showed that Ber enhanced the inhibitory effect of MMC on the viability of T24 cells. The results of flow cytometry showed that Ber also enhanced the blockade effect of MMC on T24 cells in G0/G1 phase (P<0.05). Compared with the MMC group, Ber increased the expression of p21 and p27 up-regulated by MMC, and decreased the expression of cynlin D1, CDK2 and CDK4 (P<0. 05). Meanwhile, Ber promoted MMC to inhibit the expression of survivin (P<0. 05). Ber increased the apoptosis of T24 cells induced by MMC (P<0. 05). CONCLUSION:Ber significantly enhances the inhibitory effect of MMC on the viability of T24 cells. The mechanism may be related to up-regulation of p21 and p27, thereby inhibiting the expression of cyclin D1, CDK-2 and CDK-4. At the same time, Ber inhibits the protein expression of survivin, which eventually leads to cell arrest in G0/G1 phase and promotes apoptosis.