The Effects And Molecular Mechanism Of Baicalin On Highly Invasive Breast Cancer

Background: Metastasis is thought to be the main cause of deaths in breast cancer patients,which happens partly due to the lack of effective treatment.Baicalin,a flavonoid compound isolated from the roots of Scutellaria lateriflora Georgi(Huang Qin),have recently been confirmed effective for a variety of cancers.But the effects and underlying molecular mechanisms of baicalin on metastasis of breast cancer still remain unclear.Objective: To investigate whether baicalin can inhibit the metastasis of breast cancer and to study its potential mechanism,so as to provide a new therapeutic strategy for the treatment of breast cancer.Methods:1.In vitro,the effect of Baicalin on invasion and migration of MDA-MB-231 cells and 4T1 cells were test by wound healing and Transwell assay;cell proliferation were determined by crystal violet assays.2.to evaluate the influence of baicalin on EMT process,after treated by baicalin the protein level and gene level of EMT related markers and ?-catenin in MDA-MB-231 cells and 4T1 cells were detected by immunofluorescence,Western Blot and qRT-PCR;We tested the expression of the proteins and genes again which were above-mentioned after the transfection of over-expression ?-catenin adenovirus.3.In vivo experiment,to observe the metastatic status,we established xenograft model trough using female BALB/c mice,removed the liver and lung of mice at end point,and test the expression of EMT markers and ?-catenin by immunofluorescence and immunohistochemistry respectively.Result: In this study,we found that baicalin had the potential to suppress migration and invasion of MDA-MB-231 cells and 4T1 cells in a dose-dependent manner but no influence on these cancer cells proliferation.Additionally,baicalin reversed the epithelial-tomesenchymal transition(EMT)process,as evaluated by EMT markers of the highly invasive breast cancer cell line changed from a mesenchymal feature to an epithelial type.At the same time,the expression of ?-catenin mRNA and protein was dose-dependently downregulated by baicalin in highly invasive breast cell lines,and overexpression of ?-catenin by adenoviruses abolished these beneficial effects of baicalin on migration and invasion,and EMT of breast cancer cells.Furthermore,using a xerography mice model,baicalin markedly reduced liver and lung metastasis of breast cancer,inhibited expression of ?-catenin,and degraded the EMT molecular Vimentin and Slug in orthotopic tumor tissues.Conclusion: All the experimental results show that baicalin can effectively inhibit breast cancer cell invasion and migration,and inhibit breast cancer metastasis,through downregulating the expression of ?-catenin and reversing epithelial-mesenchymal transition.