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首页> 外文期刊>Hormone and Metabolic Research >Formononetin Inhibits Migration and Invasion of MDA-MB-231 and 4T1 Breast Cancer Cells by Suppressing MMP-2 and MMP-9 Through PI3K/AKT Signaling Pathways.
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Formononetin Inhibits Migration and Invasion of MDA-MB-231 and 4T1 Breast Cancer Cells by Suppressing MMP-2 and MMP-9 Through PI3K/AKT Signaling Pathways.

机译：Formononetin通过PI3K / AKT信号通路抑制MMP-2和MMP-9，从而抑制MDA-MB-231和4T1乳腺癌细胞的迁移和侵袭。

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Formononetin is a naturally existing isoflavone, which can be found in the roots of Astragalus membranaceus, Trifolium pratense, Glycyrrhiza glabra, and Pueraria lobata. It was found to be associated with inhibition of cell proliferation and cell cycle progression, as well as induction of apoptosis in various cancer cell lines. However, the effect of formononetin on breast cancer cell metastasis remains unclear. In this study, we examined the effect of formononetin on the migration and invasion of breast cancer cells MDA-MB-231 and 4T1 in vitro and in vivo. Our data demonstrated that formononetin did not effectively inhibit the cell viability of MDA-MB-231 and 4T1 in 24?h with the concentration lower than 160?μmol/l. When treated with nontoxic concentration of formononetin, the migration and invasion of MDA-MB-231 and 4T1 cells were markedly suppressed by wound healing assay, chamber invasion assay, and in vivo mouse metastasis model. In vitro, formononetin reduced the expression of matrix metalloproteinase-2 (MMP-2), MMP-9 and increased the expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2. Furthermore, the immuno?uorescence and immunoblotting assays indicated that formononetin was very effective in suppressing the phosphorylation of Akt and PI3K. Collectively, these results suggest that formononetin inhibited breast cancer cell migration and invasion by reducing the expression of MMP-2 and MMP-9 through the PI3K/AKT signaling pathway. These findings demonstrate a potentially new therapeutic strategy of formononetin as anti-invasive agent for breast cancer.
机译：Formononetin是天然存在的异黄酮，可在黄芪、,叶，甘草和葛根的根中找到。发现与抑制多种癌细胞系中的细胞增殖和细胞周期进程以及诱导细胞凋亡有关。然而，formononetin对乳腺癌细胞转移的作用仍不清楚。在这项研究中，我们研究了Formononetin在体外和体内对乳腺癌细胞MDA-MB-231和4T1迁移和侵袭的影响。我们的数据表明，formononetin在浓度低于160μμmol/ l的24？h内不能有效抑制MDA-MB-231和4T1的细胞活力。当用无毒浓度的formononetin处理时，伤口愈合测定，腔室侵袭测定和体内小鼠转移模型显着抑制了MDA-MB-231和4T1细胞的迁移和侵袭。在体外，formononetin降低基质金属蛋白酶2（MMP-2），MMP-9的表达，并增加组织金属蛋白酶1（TIMP-1）和TIMP-2的表达。此外，免疫荧光和免疫印迹分析表明，formononetin在抑制Akt和PI3K的磷酸化方面非常有效。总体而言，这些结果表明，formononetin通过降低PI3K / AKT信号通路中MMP-2和MMP-9的表达来抑制乳腺癌细胞的迁移和侵袭。这些发现证明了formononetin作为乳腺癌抗侵袭剂的潜在新治疗策略。

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