Celecoxib antagonizes the cytotoxic effect of cisplatin in human gastric cancer cells by decreasing intracellular cisplatin accumulation

Cisplatin is a chemotherapeutic drug widely used for the treatment of gastric cancer. The benefit of including COX-2-selective inhibitors in cisplatin-based regimens on anti-cancer effect remains uncertain. In the present study, celecoxib and SC-236 antagonized cisplatin-induced cytotoxicity and apoptosis, whereas indomethancin and nimesulide exerted no effect, implying a COX-2-independent mechanism. Celecoxib decreased whole-cell cisplatin accumulation and DNA platination, resulting from reduced influx. In addition, combined treatment did not elicit greater antitumor activity than cisplatin or celecoxib monotherapy in vivo in a gastric xenograft model. Therefore, treatment strategies with celecoxib in combination with cisplatin should act cautiously.