Study On The Application And Correlation Between The Expression Of DVL3 And Extracellular Factor Beta-catenin And The Development Of Breast Cancer Cells

Objective: AMPK(Adenosine-monophosphate-activated protein kinase 5 ')is AMP dependent protein kinase,a serine / threonine protein kinase,a key molecular regulation of energy metabolism,and the main body of the energy regulatory system,to regulate and protect the cell from the outside-pressing through controlling DVL3 and ?-catenin.AMPK activators can inhibit the growth of cancer cells to achieve the effect of treatment of disease.However,the molecular mechanisms of how AMPK is activated and how to inhibit cancer cell proliferation in cancer remain unclear.We investigated the effects of AMPK activators on breast cancer cells and tissues in order to elucidate the molecular mechanism of their effects and provide reliable theoretical basis for clinical treatment.Methods: Firstly,we collected and analyzed by DVL3 and beta-catenin in 40 cases of breast cancer tissue protein expression and pathological characteristics of breast cancer by Western Blot and immunohistochemical method,and the correlation between the prognosis of different molecular subtypes.Then,we used Western Blot method to detect the expression of DVL3 and cell cycle of four kinds of breast cancer cells loaded with DVL3 plasmid or shRNA-DVL3,MCF-7,T-47 D,MDA-MB-231 and MCF-10.Then,we used the AMPK activator metformin to treat breast cancer cells in vitro,and then used the Transwell assay and the cell cloning assay to detect the development of breast cancer cells.Finally,the model of breast cancer xenografts was constructed and the expression level of DVL3 and-catenin was detected by HE staining and Western Blot method.Results: In this study,we have confirmed the overexpression of DVL3 in breast cancer tissues,and the expression of DVL3 in lymph node metastasis was significantly higher than that in primary tumors.In this paper we also found that overexpression of DVL3 and beta-catenin abnormal expression,while DVL3 overexpression and abnormal expression is associated with poor prognosis of breast cancer,and can be used as independent risk factors for the prognosis of breast cancer.In breast cancer,DVL3 can regulate the growth of cancer cells with Wnt/ beta-catenin signaling pathway.In addition,we found that AMPK activators may inhibit the growth of breast cancer cells,reduce the expression of DVL3 and Wnt/ beta-catenin signaling.Furthermore,we investigated the expression of DVL3 in breast cancer cells,and found that DLV3 is involved in cell proliferation,migration and apoptosis.AMPK activator can inhibit the growth of breast cancer cells by reducing the expression of DVL3 and decreasing the level of beta-catenin.Western blot and immunohistochemistry showed that DVL3 was significantly correlated with the expression of beta-catenin.Overexpression of DVL3 leads to an increase in the expression level of beta-catenin and excessive growth of breast cancer cells,which suggests that the activation of DVL3 through the Wnt/ beta-catenin pathway is associated with the development of breast cancer.To elucidate the mechanism,we used in vivo and in vitro AMPK activators to confirm the presence of DVL3 and beta-catenin dependence.Conclusion: The results suggest that DLV3 is not only overexpressed in breast cancer,but also can promote the proliferation,migration and invasion of breast cancer cells through the classical signaling pathway.The results of this study confirmed that AMPK activator metformin could inhibit the expression of DVL3,thereby reducing the beta-catenin,the expression of c-Myc and CyclinD1 proteins,eventually led to the proliferation of breast cancer cell migration and invasion ability was inhibited.The results of this study have a high value in clinical application,and can promote the use of metformin in the treatment of breast cancer through specific molecular mechanisms.