Department of Medical Biology, Ufuk University, Mevlana Bulvarı 86-88, 06520, Balgat, Ankara, Turkey.
ONTAL, Ufuk University, Mevlana Bulvarı 86-88, 06520, Balgat, Ankara, Turkey.
Mol Biol Rep. 2022 Jul;49(7):5973-5984. doi: 10.1007/s11033-022-07381-6. Epub 2022 Mar 30.
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.
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.
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.
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.
二甲双胍是治疗 II 型糖尿病最常用的药物之一。其抗增殖作用也被用于癌症的治疗。尽管许多研究都提到了二甲双胍抑制癌细胞增殖的积极作用，但也有一些研究对此提出了质疑。
在这项研究中，我们研究了最广泛研究的乳腺癌细胞系，ER(+) MCF7 细胞、三阴性乳腺癌 MDA-MB-231 和 MDA-MB-468 细胞在长期二甲双胍治疗下的转移行为。从 0.2 到 3.2mM 开始，MCF7、MDA-MB-231 和 MDA-MB-468 细胞获得了对二甲双胍的耐药性。
与 MCF7 和 MDA-MB-231 细胞系相比，我们仅观察到 MDA-MB-468 细胞发生了剧烈变化，其形态已向间充质样表型转变。此外，这些细胞的迁移能力也显著增加，这在 mRNA 和蛋白质水平以及划痕愈合试验中都得到了验证。除了 EMT 样表型和增加迁移能力的二甲双胍耐药 MDA-MB-468 细胞外，它们对 PI3K 抑制剂的敏感性降低。
总之，我们的数据表明，二甲双胍的作用应根据要治疗的乳腺癌亚型进行质疑。
