Metformin induces apoptosis via a mitochondria-mediated pathway in human breast cancer cells in vitro.
Metformin induces apoptosis via a mitochondria-mediated pathway in human breast cancer cells in vitro.
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DOI：
10.3892/etm.2016.3143
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发表时间：
2016-05
影响因子：
2.7
通讯作者：
Liu H
中科院分区：
文献类型：
--
作者：
Gao ZY;Liu Z;Bi MH;Zhang JJ;Han ZQ;Han X;Wang HY;Sun GP;Liu H
乳腺癌是女性最常见的癌症，也是女性死亡的第二大原因。二甲双胍是一种被广泛使用的降血糖药物，它正在成为一种潜在的癌症预防和治疗药物。然而，二甲双胍抑制癌细胞生长和诱导癌细胞凋亡的机制尚未完全阐明。本研究旨在确定二甲双胍对两种乳腺癌细胞株MDA-MB-231和MDA-MB-435的调控作用。用不同浓度的二甲双胍处理细胞，然后评估细胞的存活率、增殖、三磷酸腺苷和活性氧水平、线粒体膜电位(∆ψm)以及抗和促凋亡蛋白的表达。二甲双胍以浓度和时间依赖的方式诱导细胞凋亡，并降低细胞存活率和ATP产量。此外，二甲双胍还可诱导∆ψ-MB-231细胞产生ROS，降低MDAm，下调抗凋亡蛋白bcl2和髓系白血病1的表达，上调促凋亡蛋白bcl2相关X蛋白的表达。这些结果表明，二甲双胍对乳腺癌细胞的凋亡和细胞毒作用是由线粒体介导的内在凋亡途径介导的。
Breast cancer is the most commonly occurring cancer and second leading cause of mortality in women. Metformin is a widely prescribed anti-hyperglycemic drug, which is emerging as a potential cancer preventative and treatment agent. However, the mechanisms underlying the suppressive effects of metformin on cancer cell growth and the induction of cancer cell apoptosis are not fully elucidated. The present study aimed to identify the pathways regulated by metformin in two breast cancer cell lines, MDA-MB-231 and MDA-MB-435. Cells were treated with various concentrations of metformin and then evaluated with respect to viability, proliferation, adenosine triphosphate (ATP) and reactive oxygen species (ROS) levels, mitochondrial membrane potential (∆ψm), and the expression of anti- and pro-apoptotic proteins. Metformin caused apoptosis in a concentration- and time-dependent manner, and decreased cell viability and ATP production. Furthermore, metformin induced the generation of ROS and decreased the ∆ψm. Moreover, metformin downregulated the expression of the anti-apoptotic proteins B-cell lymphoma 2 (BCL-2) and myeloid cell leukemia-1, and upregulated the expression of the pro-apoptotic BCL-2-associated X protein in MDA-MB-231 cells. These results demonstrate that the apoptotic and cytotoxic effects of metformin on breast cancer cells are mediated by the intrinsic mitochondria-mediated apoptosis pathway.