The Study Of The Effect Of Drug7 On Melanoma Tumorgenesis And Progression In Vitro

Background:Melanoma is known as a severe disease with a steadily increased incidence and high fatality rate among all the skin cancer.Chemotherapy and biotherapy have always been the main therapeutic method for treating a cancer..Nonetheless,Chemotherapy invariability leads resistance of melanoma treatment,and the disorder of cell apoptosis is the one of the reasons that is particularly prominent in the resistance.In an attempt to remedy this situation,we have recently screened and obtained a FDA-approved candidate drug,Drug 7.This method is based on our hypothesis which is that melanoma-specific gene expression signatures could be useful for identifyingto rapidly identifying new treatments for melanoma.Such tumor-specific gene expression profiles data can be obtained from a the Connectivity Map(C-Map)database,a compendium of gene expression profiles of cancer cell lines treated with a spectrum of bioactive small molecules.In our study,we studied the therapeutic effects of Drug7 for treatment of melanoma in a human melanoma cell line A375 and explored its molecular mechanisms.Methods:The therapeutic effect has been evaluated by Caspase Apoptosis Assay,wound healing,cell invasion and migration array.The Gene Microarry and qPCR were performed to analyze the molecular mechanism of anti-tumor of Drug7.Results:The data obtained from Caspase Apoptosis Assay showed that Drug7 induced cell apoptosis of A3 75 significantly.On the other hand,the result of wound healing and cell invasion experiments suggested that Drug7 revealed a suppressing effect on cell migration,invasion as well as cell perliferation.The Microarry data indicated a series of gene which expression levels were significantly changed after the treated with Drug7.The following qPCR validation confirmed some of such genes which include some apoptosis-related genes and tumor suppressor genes,such as PDCD4,IFI44L,and several epithelial-to-mesenchymal transition response gene related to cell proliferation,migration and autoimmune diseases,e.g.CXCL5,ITGB6 and F3,and so on.Conclusion:Drug7 has a significant anti-melanoma function at a molecular level,by promoting cell apoptosis and the inhibiting cell migration,invasion and proliferation,through down-regulating and up-regulating the expression of relative genes.