Synergistic Antitumor Effect of Triptolide and Cisplatin in Cisplatin Resistant Human Bladder Cancer Cells

Purpose: We examined the synergistic antitumor effects of cisplatin combined with triptolide in cisplatin resistant T24R2 bladder cancer cells and investigated possible molecular mechanisms. Materials and Methods: T24R2 cells were treated with cisplatin and/or triptolide. Tumor cell proliferation was determined using cell counting and clonogenic assays. The combination index of the synergism between cisplatin and triptolide was calculated. The cell cycle phase and apoptosis rate were determined by flow cytometry. Apoptosis and cell cycle related protein expression were analyzed by Western blot. Results: The synergistic cytotoxicity effect of cisplatin and triptolide combination treatment was greater than the cytotoxic effect of cisplatin or triptolide alone. Combination treatment also induced cell cycle arrest via cyclin D1 and E1 expression. Apoptosis induced by combination treatment was accompanied by increased expression of caspase-3, 8 and 9, PARP and cytochrome c. Conclusions: Our results suggest that triptolide synergistically enhanced the antitumor effect of cisplatin in cisplatin resistant human bladder cancer cells. Cisplatin and triptolide combination treatment may be effective for advanced bladder cancer.