Chemoimmunosensitization of the T24 human bladder cancer line to Fas-mediated cytotoxicity and apoptosis by cisplatin and 5-fluorouracil

Previous studies have demonstrated that cisplatin (CDDP) sensitizes bladder cancer cells to Pas-mediated cytotoxicity and that CDDP also enhances the cytotoxic effect of 5-fluorouracil (5-FU). These agents mediate apoptosis a nd may share common intracellular pathways leading to cell killing. We reas oned that combination treatment with CDDP, 5-FU and anti-Fas monoclonal ant ibody (mAb) might overcome the drug-resistance. We investigated whether CDD P, 5-FU and anti-Pas mAb synergize in cytotoxicity and apoptosis against th e T24 bladder cancer line. Cytotoxicity was monitored by a one day microcul ture tetrazolium dye assay. Treatment of T24 cells with anti-Pas mAb in com bination with CDDP or 5-FU resulted in a synergistic cytotoxic effect. In a ddition, combination treatment of T24 cells with CDDP, 5-FU and anti-l;as m Ab further enhanced the synergistic cytotoxicity achieved by two agents. Th e synergy achieved in cytotoxicity with CDDP, 5-FU and anti-Fas mAb was als o achieved in apoptosis. The current study demonstrates that combination tr eatment of bladder cancer cells with CDDP, 5-FU and anti-l;as mAb overcomes their resistance. In addition, the sensitization required low concentratio ns of CDDP and 5-FU, and thus supporting the potential in vivo application of combination of CDDP, 5-FU and immunotherapy in the treatment of drug-res istant bladder cancer.