Metformin Resistant MDA-MB-468 Cells Exhibit EMT-like Phenotype and Increased Migration Capacity

Abstract Background: Metformin is one of the most prescribed drug for the treatment of type II diabetes. Its anti-proliferative effect is also taken advantage for the treatment of cancer. Despite many of the studies mention the positive effects of metformin in inhibiting the proliferation of cancer cells, there are also studies which questions this idea as well. Methods: In this study, we investigated the most widely studied breast cancer cell lines, ER(+) MCF7 cells, TNBC MDA-MB-231 and MDA-MB468 cells in terms of metastatic behavior under long-term metformin treatment. MCF7, MDA-MB231 and MDA-MB468 cells were gained resistant to metformin starting from 0.2mM to 3.2mM. Results: Compared to MCF7 and MDA-MB231 cell lines, we only observed dramatic changes in MDA-MB468 cells whose morphology has been changed towards mesenchymal like phenotype. Moreoever, migration capacity of these cells were also significanlty increased which were validated at both mRNA and protein levels as well as wound healing assay. In addition EMT like phenotype and increasing migration capacity of metformin resistant MDA-MB468 cells, they exhibited less sensitivity to PI3K inhibitor. Conclusions: All together, our data pointed out that, metformin’s effects should be questioned depending on the subtype of the breast cancer that’s to be treated.