Glabridin Attenuates The Migratory And Invasive Capacity Of Breast Cancer Cells By Activating MicroRNA-200c

The prevention of nutrients and bioactive substances in food on chronic disease has become the key area in the preventive medicine research. In chronic. disease, cancer invasion and metastasis are the leading causes of death. The inhibition of tumor invasion and metastasis by glabridin(GLA) was still unknown. In the present study, the invasive human breast cancer cells (MDA-MB-231and BT549breast cancer cells) and MDA-MB-231breast cancer xenografts were used as a model to investigate the mechanism of GLA on migration and invasion in vitro and in vivo. This study will provide more evidences for the prevention of breast cancer by GLA.Objective:The invasive human breast cancer cells (MDA-MB-231and BT549breast cancer cells) and MDA-MB-231breast cancer xenografts were used as a model to investigate the mechanism of GLA on breast cancer cell migration and invasion in high invasive human breast cancer cells.Methods:By MTS assay,we detected the proliferation of MDA-MB-231and BT549breast cancer cells;The inhibition of invasion, metastasis by GLA were observed with wound-healing asssay and transwell assay; the expression of epithelial and mesenchymal markers adhesion molecules weredetected by Western blotting and RT-PCR assay; Effects of GLA in the expression of miR-200c was detected by Real time PCR assay. By transfections of miR-200c-mimic and anti-miR-200c,we abserved the effects of glabridin on the inhibitions of the migratory and invasive capacity of breast cancer cells by activating miR-200c.Xenograft experiments were used to explore whether GLA could inhibit tumor growth, metastasis and invasion in vivo.Results:Through MTS assay,we found that both MDA-MB-231and BT549cells at a concentration of less than20^M GLA treated, the vitality of the cells are not affected; By wound-healing assay, we found that (GLA) treated invasive breast cancer cells MDA-MB-231and BT549enhanced the inhibitory effect of motility capacity in a dose-dependent manner;Further experiments using transwell assay found that GLA could significantly inhibit the migration and invasion of MDA-MB-231and BT549cells; RT-PCR and Western blotting results showed GLA can induce the expression of E-cadherin on mRNA and protein levels; while reducing mesenchymal marker Vimentin on mRNA and protein levels. Real time PCR results displayed that in MDA-MB-231and BT549cells,GLA upregulated the expression of miR-200c; high expression of miR-200c increased the expression of E-cadherin level, but transfected anti-miR-200c can reduce the expression of E-cadherin level,and attenuate the inhibition capacities of invasion and migration by GLA.In vivo, RT-PCR and Western blotting results also showed GLA can induce the expression of E-cadherin; while reducing the expression of Vimentin and upregulate the expression of miR-200c.Conclusion:GLA could significantly inhibit the invasion and migration of high invasive breast cancer cells MDA-MB-231and BT549which induces expression of E-cadherin by activating miR-200c. Therefore, miR-200c/E-cadherin may be an important mechanism participated in inhibition of invasion and migration by GLA.