Effects of the Specific COX-2 Inhibitor, Celecoxib, on Paclitaxel-Induced Apoptosis in SK-OV-3 Epithelial Ovarian Cancer Cell Line.

Objective: In vitro studies have revealed that treatment of various human cancer cell lines with specific cyclooxygenase 2 (COX-2) inhibitors induces apoptotic cell death. The goal of this article is to investigate the benefits of combining COX-2 inhibitors with existing treatment modalities in the management of ovarian cancer. Methods: In this study we sought to determine the effects of combining paclitaxel and the COX-2 inhibitor celecoxib on apoptosis of epithelial ovarian cancer (EOC) cells. SK-OV-3 cells were exposed to increasing concentrations of paclitaxel ( M, M and M) and celecoxib ( M, M, M, M and M) as well as a combination of both drugs. The activity of apoptosis was evaluated by the morphologic examination and the MTT assay. The pattern of apoptosis was also assessed by the caspase-3 activity and the fraction of cleaved PARP (poly ADP-ribose polymerase) protein. Results: Single application of both drugs could significantly increase the rate of apoptosis after 24 hours of continuous exposure. But concomitant treatment of SK-OV-3 EOC cell line with paclitaxel and celecoxib resulted in marked impairment of paclitaxel-induced apoptosis. The pattern of apoptosis induced by paclitaxel on SK-OV-3 EOC cell line was caspase-3 independent. Conclusion: Combining COX-2 inhibitors and paclitaxel does not have an additive or synergistic tumoricidal effect. On the contrary, celecoxib treatment markedly inhibited the apoptotic effects of paclitaxel in SK-OV-3 EOC cell line.