Effect of metformin on apoptosis induction in ovarian cancer cells

Introduction: Ovarian cancer is one of the most difficult problems in gynecologic oncology and the search for new drugs effective in the treatment of this kind of cancer, especially in cases resistant to current forms of therapy, remains a challenging priority.

The aim of the study was to analyze the effect of metformin on apoptosis and the BIRC5 gene expression in ovarian cancer cell line SKOV-3. The BIRC5 gene encodes survivin protein.

Material and methods: SKOV-3 cells were treated with metformin (10 mM). Apoptotic changes in studied cells were analyzed by double staining using a mixture of fluorochromes – Hoechst 33258/propidium iodide (PI). The expression of the BIRC5 gene at the mRNA level was analyzed using the real-time PCR technique.

Results: Treatment of cells with metformin causes changes in the cell shape from oval to spindle and leads to the separation of the cells from the monolayer. Furthermore, metformin induces apoptosis and necrosis of ovarian cancer cells. A statistically significant increase in the number of apoptotic cells after 48 and 72 hours’ treatment with metformin relative to a control cells seems to be correlated with a decrease in the expression of the BIRC5 gene at the mRNA level.

Conclusions: Metformin seems to be a promising agent, whose use in ovarian cancer patients may contribute to improving the effectiveness of therapy.