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.