Celecoxib Potentiates the Anticancer Effect of Cisplatin on Vulvar Cancer Cells Independently of Cyclooxygenase

Abstract

Cyclooxygenase-2 (COX-2) has been found to be associated with the development and progression of various cancers. Our previous study showed a high expression rate of COX-2 in paraffin-embedded tissue specimens from patients with vulvar cancer. In this study, we evaluated the efficacy of celecoxib, a selective COX-2 inhibitor, as a chemosensitizing agent with cisplatin in vulvar cancer cells A431 and SW962. COX-2 was expressed in both A431 and SW962 vulvar cancer cell lines. COX-1 was expressed in A431 but not in SW962. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide] assay showed that treatment with 30 mu mol/L celecoxib had no effect on cell growth in A431 cells for 72 h. However, combined treatment with celecoxib and cisplatin induced a significant reduction in cell growth compared to single treatment with cisplatin. Interestingly, single treatment with celecoxib or cisplatin and combined treatment of 10 mu mol/L celecoxib with 10 mu mol/L cisplatin increased COX-2 expression. However, the combination of 30 mu mol/L celecoxib and 30 mu mol/L cisplatin reduced COX-2 expression to the control state. Inhibition of cell growth by celecoxib alone and in combination with cisplatin was independent of the expression level of COX-2 induced by these agents. While treatment with 10 mu mol/L celecoxib or 10 mu mol/L piroxicam significantly suppressed the activity of COX enzymes, neither agent affected the growth of A431 and SW962 cells at this concentration. Taken together, celecoxib could be used as a chemosensitizing agent in vulva cancer cells; the anticancer activity of celecoxib seemed to be independent of COX.