DSG2 Knockdown Increase The Paclitaxel Chemosensitivity In Ovarian Cancer Cells

Objective:Ovarian cancer r,as a common gynecological malignant tumor,ranks eighth among female lethal carcinoma in the world,which severely women’s threatens life and health.Currently,the standard treatment for ovarian cancer is cytoreductive surgery followed by the combination of paclitaxel and platinum-based chemotherapy.Approximately 80%of patients can obtain clinical remission,but majority of which will relapse because of chemoresistance.It is suggested that DSG2 is related to paclitaxel-resistance ovarian cancer cell lines.DSG2,the member of desmosomal cadherin family,is an important protein that constitutes desmosomes.It is implicated in intercellular adhesion and abnormally express in multiple tumors,which closely related to tumor dedifferentiation,migration and invasion.We performed this study to explore the molecular mechanism of DSG2 in paclitaxel-resistant ovarian cancer cells.Methods:1.Using the drug step-by-step method to construct paclitaxel-resistance cell lines A2780/Taxol and ES2/Taxol;2.Using crystal violet assay to verify the paclitaxel resistance of ovarian cancer cells and corresponding drug-resistance cells(A2780/Taxol and A2780,ES-2 and ES2/Taxol);3.Using qRT-PCR and western blotting to detect the level of DSG2 expression in ovarian cancer cell lines and corresponding drug-resistance cells;4.After transfecting DSG2-siRNA in A2780/Taxol and ES2/Taxol,western blotting was used to examined the expression of DSG2,and crystal violet assay was used to measure the change of IC50 value after dealing with different concentrations of paclitaxel;5.Western blotting was used to detect the expression of ABCB1 after transient transfection of DSG2-siRNA.Results:1.Successful construction of paclitaxel-resistance ovarian cancer cell lines.2.DSG2 expression increased in paclitaxel-resistance ovarian cancer cell lines(A2780/Taxol and ES2/Taxol)(P<0.05).3.Inhibiting DSG2 in paclitaxel-resistance ovarian cancer cell lines(A2780/Taxol and ES2/Taxol)resulted in the decreased IC50 value of cells(P<0.05),drug resistance and ABCB1 expression(P<0.05).Conclusions:1.Compared with the parental cells,DSG2 expression in paclitaxelresistance ovarian cancer cell lines(A2780/Taxol and ES2/Taxol)was upregulated.After silencing DSG2,the IC50 value of drug-resistance cell lines decreased,and the sensitivity to paclitaxel improved,implying that DSG2 was involved in the regulation of paclitaxel resistance in ovarian cancer cells;2.After knocking down DSG2,ABCB1 expression in A2780/Taxol and ES2/Taxol decrease,implicating that DSG2 may affect the resistance to paclitaxel in ovarian cancer cell lines by regulating the expression of ABCB1.