Antitumor Activity of Metformin in Combination with Binimetinib Against Melanoma Cells

Malignant melanoma is skin cancer with high metastatic potential and resistance to treatment. Significant progress has been made following the introduction of its treatment kinase inhibitors such as binimetinib. Some studies suggested that the combination of metformin with BRAF/MEK inhibitors suppresses cancer cell growth and progression. This study aimed to assess the impact of metformin and binimetinib, both individually and in combination, on the growth, proliferation, and apoptosis of melanoma cells in vitro. The study also sought to predict potential interactions between metformin and binimetinib when co-administered employing in silico analysis. Cell growth and proliferation of melanoma cells exposed to metformin and binimetinib, alone and in combination, were determined by SRB and BRDU assays. Further investigations were performed using real-time RT-qPCR and ELISA method. These results revealed that the simultaneous use of metformin and binimetinib exerted an additive or synergistic inhibitory effect on melanoma cell growth. The concomitant effect of both compounds depended on the concentrations used and was caused by the reduced proliferation and/or increased apoptosis of melanoma cancer cells. In conclusion, the combination of metformin and binimetinib may have potential anticancer effects on melanoma cells; however, more studies are needed to elucidate the exact mechanisms of their combined action.