Metformin resistant MDA-MB-468 cells exhibit EMT-like phenotype and increased migration capacity

Abstract

Purpose Metformin is one of the most prescribed drugs 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 mentioning 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-MB-468 cells in terms of metastatic behavior under long-term metformin treatment. MCF7, MDA-MB-231 and MDA-MB-468 cells were gained resistant to metformin starting from 0.2 to 3.2 mM. Results Compared to MCF7 and MDA-MB-231 cell lines, we only observed dramatic changes in MDA-MB-468 cells whose morphology has been changed towards mesenchymal like phenotype. Moreover, migration capacity of these cells was also significantly increased which were validated at both mRNA and protein levels as well as wound healing assay. In addition to EMT like phenotype and increasing migration capacity of metformin resistant MDA-MB-468 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.