Synergistic Effects of Metformin-Lapatinib Combination on the Expression of Bax in SK-BR3 Cells

Abstract

Background: HER2-positive breast cancers tend to be more aggressive and are associated with poorer outcomes than other types of breast cancer. Metformin, the first-line medication for the treatment of type 2 diabetes, has anticancer activity against various cancerous cells. Objectives: We assessed the cytotoxic effect of metformin in combination with Lapatinib on the SK-BR3 cells. Methods: Following culturing cells, IC50 of metformin and lapatinib were calculated using MTT assay after 48h of treatment with different concentrations of metformin and lapatinib alone and in combination. The level of pro-apoptotic protein Bax expression was measured by western blot analysis. Results: Metformin and lapatinib could significantly inhibit the cell viability of SKBR-3 in a dose-dependent manner, and the minimum cytotoxic effect of these drugs was observed after 48 h at 5 mM and 50 nM, respectively. Several combinations of metformin with lapatinib showed a synergistic efficacy on the cell viability inhibition, which could decrease the IC50 of lapatinib from 500 nM to at least 200 nM. The strongest synergistic cytotoxic effect on the cell viability was observed at 40 mM of metformin plus 400 nM of lapatinib. Furthermore, after 48h of co-treatment with metformin-lapatinib combination, the level of pro-apoptotic Bax expression was significantly increased at 10 mM of metformin plus 200 nM of lapatinib. Conclusions: This study demonstrated that the metformin-lapatinib combination may be a valuable candidate for breast cancer patients with HER2 overexpression. However, further studies are needed to make a definitive conclusion.