Repurposing celecoxib for ovarian cancer treatment by targeting survivin signaling

Abstract

Abstract Background Ovarian cancer is the leading cause of deaths among gynecologic cancers. With a five-year survival rate just slightly above 45% and high rates of chemo-toxicity and chemo-resistance, the search for novel, more effective, and less toxic therapeutic approaches is thus imperative. In the current study, we aimed to explore the potential antitumor effect of a COX-2 inhibitor, celecoxib, using a panel of ten ovarian cancer cell lines derived from varying histology. Methods We analyzed anti-proliferative effect of celecoxib by cell viability assay using WST-8 (water-soluble tetrazolium salt solution). The compound’s effect on cell cycle progression and apoptosis were evaluated by flow cytometry. Western blotting was employed to explore its influence on apoptosis-related genes. Results Celecoxib significantly and, in a dose-dependent manner, inhibited proliferation of all analyzed ovarian cancer cell lines at IC50 ranging from 17µm ~ 45µm irrespective of their histological characteristics, arrested the cell cycle, and induced apoptosis (p < 0.001, treated vs. DMSO). Further exploration revealed that treatment of the cells with celecoxib caused cleavage of caspase-3 and down-regulation of survivin, the effects that were comparable across all analyzed cell lines and independent to autophagy. Conclusions The findings confirm the antitumor effect of celecoxib against a panel of ovarian cancer cells of varying histology by targeting the anti-apoptotic protein, survivin, and suggest that this may serve as a novel targeted therapeutic approach for ovarian cancer. Large-scale clinical trials are therefore warranted to further evaluate its efficacy, and for optimization.