Abstract
As a cyclooxygenase-2 inhibitor, the potential of celecoxib, to enhance the efficacy of chemotherapy is being investigated in clinical trials related to cancer treatment. In this study, we investigated whether celecoxib would increase the anti-proliferative effects of cisplatin in human lung cancer cell lines. The results demonstrated the synergistic effects of celecoxib with cisplatin in wild-type p53 cells and their antagonistic effects in mutated or deleted p53 cells. Combination indices of 0.82–0.93 reflected a synergistic effect between celecoxib and cisplatin in lung cancer cells with wild-type p53. Combination indices of 1.63–3.00 reflected antagonism between celecoxib and cisplatin in lung cancer cells with mutated or deleted p53. Apoptosis was shown to increase with the addition of celecoxib and cisplatin. Apoptosis was accomplished by the downregulation of slug expression. Celecoxib increased the nuclear localization of active p53 in lung cancer cells of wild-type p53. Taken together, our data demonstrated clear synergistic effects in wild-type p53 cells and antagonistic effects in mutated or deleted p53 cells when celecoxib and cisplatin are combined.
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