Activation Of Hippo Signaling Pathway Is Involved In Metformin Inhibition Of Breast Cancer MCF-7 Cell Growth

Aims:Metformin is a first-line treatment for type 2 diabetes,especially in patients with poor glycemic control after simple diet control or regular exercise.Metformin has effect on reducing the risks of cancer development,especially the breast cancer.In this study,the antitumor effect of metformin was verified by using MCF-7 cells,and to investigate whether Hippo signaling pathway can be used as a potential molecular target for metformin-mediated anti-tumor activity.Methods:1)MCF-7 cells intervene by metformin or not.2)We counted by hemocytometer.The cell proliferation was detected by Cell Counting Kit-8 method.3)We use flow cytometry to detect the cell cycle and apoptosis.4)The changes of ability of migration were detected by scratch-healing test.5)The expression of YAP?Yes-associated protein?1,MST?Macrophage-stimulating protein?1 and LATS?Large Tumor Suppressor Kinase?1 were detected by RT-PCR6)Western blotting was used to detect the expression of YAP1,phosphorylated YAP1?p-YAP1?and LATS1.,respectively.Results:1)Metformin significantly increased the inhibition rate of cell proliferation in MCF-7 cells in a concentration-dependent and time-dependent manner,the difference among different groups was statistically significantly.2)The half inhibition concentration(IC₅₀)of metformin in the MCF-7 cells was about 40mmol/L.3)Metformin resulted in the cells cycle of MCF-7 to block in the G₀/G₁ phase.4)Metformin treatment significantly induced apoptosis of MCF-7 cells5)Metformin treatment significantly inhibited cell migration.6)Metformin treatment significantly increased the mRNA expressions of YAP1,LATS1,MST1.7)Upon metformin treatment,there were significantly reduction in the protein expressions of YAP1,LATS1,MST1,but up-regulated the p-YAP1 expression.Conclusions:The findings in our study suggested that the proliferation of MCF-7cells could been inhibit by metformin.Metformin induce the late apoptosis of MCF-7cells.The activation of Hippo pathway plays an important role in the above process.A useful foundation for further studies about the application of Hippo pathways was given by our data,especially in the treatment of breast cancer.