Background: There is controversy on the safety of inhibitors of cyclooxygenase administered at high doses; however, these drugs have been reported to be effective in the prevention of a variety of human cancers. To determine if celecoxib influences cellular growth, we evaluated several effects in ovarian carcinoma cell lines.
Methods: CAOV3, OVCAR3 and SKOV3 cell lines were exposed to different concentrations of celecoxib (0-100 microM) for 24-96 h. Cellular growth was assessed using a cell viability assay. Immunohistochemistry was performed to evaluate Ki-67 and cleaved caspase-3. Apoptosis was determined by a TUNEL assay, and Western blot was used to determine COX-2 protein expression.
Results: We observed a significant decrease in the cellular growth of all cell lines studied exposed to > or = 70 microM of celecoxib for 72 and 96 h (p < 0.02). All cells demonstrated pancytotoxicity at 100 microM of celecoxib. A significant decrease in Ki-67 expression in all cell lines exposed to > or = 30 microM of celecoxib (p < or = 0.05) for 72 h was observed. We observed significant changes in apoptosis and cleaved caspase-3 expression in SKOV3 cells exposed to 50 microM of celecoxib. Downregulation of COX-2 protein expression caused by celecoxib was observed in SKOV3 cells.
Conclusions: We found that celecoxib inhibits cellular growth and proliferation in a dose-dependent manner in all cell lines studied. SKOV3 cells showed an increase in cleaved caspase-3 expression. Additional studies are in progress to evaluate the effects of celecoxib on other aspects of the control of the cell cycle in cancer cells.