黄豆苷元促进乳腺癌细胞增殖、侵袭和迁移的机制研究

A study on mechanism of daidzein to promote proliferation,invasion and migration of breast cancer cells

目的探讨黄豆苷元对乳腺癌MCF-7和MDA-MB-231细胞增殖、迁移和侵袭等生物学行为的影响及其相关机制。方法体外培养乳腺癌MDA-MB-231、MCF-7细胞,应用CCK-8实验、平板克隆形成实验、细胞划痕实验以及Transwell实验,检测不同浓度黄豆苷元(0、40、80、160μmol/L)对乳腺癌细胞的活力、克隆形成能力、迁移与侵袭的影响;应用Western Blot法检测乳腺癌细胞中Wnt/β-catenin信号通路相关蛋白(Wnt-3a,β-catenin)和上皮—间质转化(EMT)相关蛋白[E-cadherin、Vimentin、Slug、Twist]的表达。结果黄豆苷元对乳腺癌MDA-MB-231、MCF-7细胞的活力有明显抑制作用且呈剂量依赖关系(P<0.05);随着黄豆苷元浓度增加,乳腺癌细胞的克隆形成能力逐步降低,迁移、侵袭能力逐渐减弱(P<0.05)。黄豆苷元的干预显著提高乳腺癌细胞E-cadherin表达水平,降低β-catenin、Wnt-3a、Vimentin、Slug、Twist蛋白表达水平(P<0.05)。结论黄豆苷元可能通过影响细胞Wnt/β-catenin信号通路相关蛋白和EMT相关蛋白的表达,抑制乳腺癌细胞MCF-7和MDA-MB-231的增殖、侵袭和迁移能力,进而抑制肿瘤的发展。

Objective To investigate the effects of daidzein on proliferation,migration and invasion of breast cancer cell line MCF-7 and MDA-MB-231 and its related mechanisms.Methods Breast cancer MDA-MB-231 and MCF-7 cells were cultured in vitro.The effects of daidzein at different concentrations(0,40,80,160μmol/L)on the viability,colony forming ability,migration and invasion of breast cancer cells were detected by CCK-8 test,plate clone formation test,cell scratch test and Transwell assay.The expression of Wnt/β-catenin signaling pathway related proteins(Wnt-3a,β-catenin)and epithelial-mesenchymal transition(EMT)related proteins(E-cadherin,Vimentin,Slug,Twist)in breast cancer cells were detected by Western Blot.Results Daidzein significantly inhibited the viability of breast cancer cells MDA-MB-231 and MCF-7 in a dose-dependent manner(P<0.05).With the increase of daidzein concentration,the clone formation ability,migration and invasion ability of breast cancer cells decreased gradually(P<0.05).The expression level of E-cadherin in breast cancer cells increased,while the protein expression levels ofβ-catenin,Wnt-3a,Vimentin,Slug and Twist decreased significantly by the intervention of daidzein(P<0.05).Conclusion Daidzein may inhibit the proliferation,invasion and migration of breast cancer cells MCF-7 and MDA-MB-231 by affecting the expression of Wnt/β-catenin signaling pathway-related proteins and EMT-related proteins,thus inhibit tumor development.