β-Lapachone对乳腺癌细胞增殖、迁移和凋亡的作用及机制

Effect of β-Lapachone on the proliferation,migration and apoptosis ability of breast cancer cells and mechanism

目的:探索β-Lapachone与乳腺癌细胞MCF-7和MFM223的细胞增殖、迁移和凋亡作用及机制。方法:采用β-Lapachone以不同浓度处理乳腺癌细胞MCF-7和MFM223,不同时间点后,进行MTT,细胞克隆实验,细胞增殖毒性实验,划痕实验,观察给药后对细胞的增殖和迁移能力,凋亡实验验证给药后对乳腺癌细胞的凋亡作用,Western blot实验检测迁移和凋亡相关蛋白的表达水平。结果:与对照组相比,β-Lapachone给药后乳腺癌细胞增殖,迁移能力随着浓度的增加而降低,凋亡相关蛋白水平与β-Lapachone给药浓度呈正相关,细胞中迁移相关蛋白(MMP-2/9、Ezrin、vimentin、Snail、GSK-3β)表达明显下调(P<0.05),凋亡相关蛋白(Caspase-3/8/9)明显上调,BCL-2/Bax的比值下降(P<0.05)。结论:β-Lapachone能够有效抑制乳腺癌细胞增殖能力,通过EMT途径抑制乳腺癌细胞迁移,Caspase依赖途径诱导乳腺癌细胞的凋亡。

Objective:To investigate the effects ofβ-Lapachone on proliferation,migration and apoptosis in breast cancer cells(MCF-7 and MFM223)and its mechanism in vitro.Methods:The cell viability was detected using MTT,colony formation assay.The migration ability was determined using scratch assay method,and the apoptosis was examined using flowcytometry.Meanwhile,the expression of biomarkers of proliferation,EMT markers and apoptosis were detected using Western blot analysis.Results:β-Lapachone could significantly inhibit the proliferation of MCF-7 and MFM223 breast cancer cells(P<0.05).β-Lapachone could also inhibit the migration and motility of breast cancer cells via down-regulating the expression levels of MMP-2/9 and Ezrin proteins and up-regulating the epithelial markers.In addition,β-Lapachone enhanced the apoptosis of breast cancer cells,down-regulated BCL-2/Bax ratio and up-regulated of activated Caspase-3/8/9.Conclusion:β-Lapachone can effectively inhibit the proliferation and induce the apoptosis of breast cancer cells,and inhibit the migration of gastric cancer cells via MMPs and EMT pathways.