A New Insight Into the Anti-Proliferative and Apoptotic Effects of Betatrophin on Human Ovarian Cancer Cell Line Skov-3

Objective: Ovarian cancer is one of the most common and deadly cancers in women; it has a high resistance to treatment, emphasizing the need for a new therapeutic approach. In the present study, the effect of betatrophin, a protein member of the ANGPTL family, on the expression of BAX and Bcl-2 genes in the apoptosis pathway in the ovarian Skov-3 cell line was investigated. Methods: The Skov-3 ovarian cell line was treated with different betatrophin concentrations for 48, 72, and 96 hours. The MTT assay was utilized to investigate the viability of cells after treatment, and the apoptotic-inducing effect of betatrophin was evaluated by Annexin V/ propidium iodide double staining. Quantitative real-time PCR was used to determine the expression level of BAX and Bcl-2 genes. Results: According to the findings, betatrophin was able to reduce the viability of Skov-3 cells and thus prevent their development. This effect was shown to be concentration and time dependent with IC50 being 930.7, 811.4, and 761.5 ng/mL for 48, 72, and 96 hours, respectively. Additionally, betatrophin decreased Bcl-2 anti-apoptotic protein expression and increased BAX pro-apoptotic protein expression. Conclusion: The obtained results suggested the ability of betatrophin to induce apoptosis via its cytotoxic effects on Skov-3 cell lines at higher concentrations through affecting the BAX/Bcl-2 expression ratio.