Effects And Mechanisms Of Quercetin On Breast Cancer Cells Via The Hippo-Yap Signaling Pathwa

Background:Breast cancer has become the world’s highest incidence and mortality of new cancers in women.Although modern molecular diagnostic techniques are advancing rapidly,different molecular types of breast cancer can be optimized for treatment.However,due to the lack of corresponding hormone receptor expression in HER2-positive breast cancer,it is difficult for general endocrine therapy to achieve the expected therapeutic effect,and targeted drug therapy is still the main therapeutic means.At the same time,the discovery of drug resistance in the course of drug therapy is one of the difficult problems to be solved urgently.The effect of TCM in clinical antitumor therapy has been recognized more and more,and it has been found to have unique clinical advantages such as low toxicity and side effects in clinical treatment practice.Pharmacological research technology related to modern medicine is advancing rapidly.Traditional Chinese medicine plays an irreplaceable role in the treatment of breast cancer.It is one of the research focuses of modern medicine to find traditional Chinese medicine substances with good therapeutic effect and small side effects.Quercetin,as a widely existing Chinese herbal flavonoid,has anti-tumor,anti-inflammation,antibacterial and cardiovascular protective effects.Studies have shown that quercetin can reverse adriamycin resistance in breast cancer cells through GSK-3β-β-catenin signaling pathway mediated by GAS5.Hippo signaling pathway exists widely in vivo,is one of the signaling pathways involved in breast cancer metastasis,and plays an important role in cell proliferation and apoptosis.Quercetin has the potential ability of regulating Hipo-Yap signaling pathway to reverse drug resistance in breast cancer cells,but the specific mechanism of action needs further study.Objective:To investigate whether quercetin inhibits breast cancer MCF7 cells and whether quercetin inhibits breast cancer SK-BR-3 cells through the Yap-mediated Hippo signaling pathway,and whether it can improve breast cancer drug resistance and enhance its therapeutic effect,in response to the difficult problem of drug resistance in breast cancer in the clinic.Methods:MCF7 and SK-BR-3 cells were used for in vitro experiments.The cell activity of MCF7 cells treated with quercetin at different concentrations(23.75.47.5,95,190 μmol/L)was determined by CCK-8 method.The cell activity of SK-BR-3 was determined under the intervention of quercetin.Flow cytometry was used to detect the apoptosis rate of breast cancer MCF7 cells treated with quercetin at different concentrations(23.75,47.5,95,190μmol/L).The apoptosis rate of breast cancer SK-BR-3 cells treated with quercetin was determined.The expressions of MEK1,RAS and YAP in MCF7 cells treated by quercetin were detected by western blot.The protein expressions of PI3kp85,p53,p73,PTEN,Yap,Taz,Mek1,HER1,HER2 and HER4 in breast cancer SK-BR-3 cells under quercetin intervention were determined.ER and PR staining were observed by immunofluorescence staining and quantitative analysis,and the average fluorescence intensity was analyzed by ImageJ180 after photography.Results:Quercetin can inhibit the activity of breast cancer MCF7 cells,and this inhibition is concentration-dependent,not time-dependent;with the increase of quercetin concentration,the late apoptosis rate of breast cancer cells MCF7 increased significantly;quercetin can increase the expression of ER and PR in MCF7 cells;quercetin can inhibit the cellular activity of breast cancer SK-BR-3;quercetin can reduce the expression of Yap,Mek1,HER1 and other proteins,and has no significant inhibitory effect on the expression of p53,p73,PTEN,HER4 and other proteins.Conclusion:Quercetin can inhibit the activity of breast cancer MCF7 cells,and this inhibition is concentration-dependent,not time-dependent;with the increase of quercetin concentration,the late apoptosis rate of breast cancer cells MCF7 increased significantly;quercetin can increase the expression of ER and PR in MCF7 cells;quercetin can inhibit the cellular activity of breast cancer SK-BR-3;quercetin can reduce the expression of Yap,Mek1,HER1 and other proteins,and has no significant inhibitory effect on the expression of p53,p73,PTEN,HER4 and other proteins.