The cytotoxic effect,cell cycle perturbations and apoptosis of paclitaxel in human bladder cancer lines

Purpose:To determine the efficacy of paclitaxel in human bladder cancer lines and to investigate the mechanism by which paclita xel induce apoptosis in human bladder cancer cells. Methods:BIU-87, 5637, T24 and EJ bladder cancer cell lines wer e cultured by techniques of cell culture in vitro. The cytotoxic activity an d apoptosis induction abilities of paclitaxel were analyzed by MTT and Annexin- V assay as well as DNA cytometry , respectively. The effects on the cell cycle w ere assessed by flow cytometry of propidium iodide. The expressions of Bcl-2, B ax, p53 and Caspase3 proteins were determined by flow cytometry immunofluorescen ce. Results:Paclitaxel dose-dependent inhibition of cell prolifera tion was seen.Paclitaxel induced G_2/M arrest (71.29% and 64.57%) which was maximal in 5637 and EJ cell lines. While paclitaxel at 1μg/ml concentration ex posure to 5637 12h, 14h and 48h respectively, the apoptosis rates of the respect ive times were 5.0%, 12.9%, 27.6%. The expression of genes p53 and Bcl-2 was no t influenced, whereas the expression of Bax and Caspase3 had increases time-dep endently after exposure to paclitaxel. The analysis of Annexin-V showed a drama tic dose-dependent increase of apoptosis. Conclusions:Paclitaxel inhibited bladder cancer cells prolifera tion and had more effect on those cells whose grade was lower and doubling time was longer. Paclitaxel could block G_2/M arrest, and induce apoptosis by th e path of Bcl-2/Bax in bladder cancer cell lines.