EXAMINING THE EFFECT OF METFORMIN ON ENHANCING THE SENSITIVITY OF CISPLATIN-RESISTANT OVARIAN CANCER CELLS (A2780/CP)

Cancer is considered as one of the main causes of death and a major health challenge in the world. Resistance to chemotherapy is one of the challenges in this field. Some recent findings have shown that anti-diabetic drugs, especially metformin, when combined with anticancer drugs, produce positive effects in cancer treatment. In the present study, the activity and possible mechanism of the effect of metformin in increasing the sensitivity of ovarian carcinoma cell line A2780/CP to cisplatin were investigated.

In this experimental study, ovarian cancer cells resistant to cisplatin (A2780/CP) were selected. The effect of metformin on cisplatin cytotoxicity was evaluated using MTT method. The mRNA expression levels of multidrug resistant-associated protein 2 (MRP-2) after metformin treatment were determined using reverse transcription polymerase chain reaction (RT-PCR). The effect of metformin on cisplatin-induced apoptosis was investigated using the Annexin V/FITC method. All data were analysed using GraphPad Prism 6.01, and p value < 0.05 were considered as significant.

Metformin increased the cytotoxic effects of cisplatin in cisplatin-resistant A2780/CP ovarian cancer cells, but had no effect on the cytotoxicity of sensitive A2780 ovarian cancer cells. Metformin had no effect on MRP-2 gene expression. In addition, metformin increased the apoptotic effects of cisplatin in A2780/CP cells.

The results of the present study showed that metformin increases the sensitivity of A2780/CP cells to the cytotoxic effects of cisplatin. Therefore, metformin may be an effective and potent compound for combination therapy in ovarian cancer cells to overcome multidrug resistance to chemotherapy agents.