Effect Of ZEB1 Gene Expression On Its Cellular Phenotype And Antiandrogen Sensitivity In Prostate Cancer

ObjectiveAnti-androgen drug therapy is one of the main treatments for prostate cancer,most patients are prone to develop drug resistance after treatment,and develop into castrated and resistant prostate cancer(CRPC),leads to further disease progression,but the resistance mechanism is unknown.Studies have shown that ZEB1 can directly bind to AR and regulate its changes.What is the relationship between ZEB1 and AR in prostate cancer tissues? Is the regulation of ZEB1 expression related to anti-androgen drug resistance,It’s worth further study.This study aims to explore the mechanism of ZEB1 expression in prostate cancer cells in CRPC and provide new ideas for drug therapy of prostate cancer.MethodThe clinical data of 47 patients with prostate cancer hospitalized in the Department of Urology of the 940 Hospital of China Joint Logistics support Force from November 2013 to June 2021 were analyzed retrospectively,and the expressions of ZEB1,AR,E-Ca and N-Ca were detected by immunohistochemical staining,and the differences in expression among different risk groups,TNM stage and Gleason score were compared and analyzed,as well as the relationships among the above four proteins.Lentivirus interference or overexpression was performed on prostate cancer cell lines to observe their cell biological behavior and analyze the effects of ZEB1 expression regulation on the proliferative activity,invasion,migration and drug resistance of prostate cancer cells.ResultIn histopathological studies,the positive expression rate of ZEB1 increased with the increase of risk score,Gleason score and PSA value,while the strong positive expression rate of AR decr-eased with the increase of risk degree and Gleason score,the positive expression rate of E-Ca decreased with the increase of risk score,Gleason score and PSA value,while the positive expression rate of N-Ca increased with the increase of risk score and Gleason score.The positive expression rate of ZEB1 increased with higher tumor stage and TNM stage,the strong positive expression rate of AR decreesed only with increasing TNM stage,Patients whose first surgical specimen had a higher expression level of ZEB1 were more easy to develop into CRPC.Compared with DU145 cell line in control group,DU145 cell line interfered with ZEB1 significantly decreased cell proliferation,invasion,migration and drug resistance,while22RV1 cell line overexpressing ZEB1 significantly increased cell proliferation,invasion,migration and drug resistance compared with 22RV1 cell line in control group.Concludion1.In prostate cancer tissues,it is suggested that ZEB1 may directly affect the occurrence and development of prostate cancer through AR,and ZEB1 may also be related to the occurrence and development of CRPC.2.In prostate cancer cells,regulation of ZEB1 can change cytological function.As an inducer of EMT,ZEB1 promotes the proliferative activity,migration and invasion ability of prostate cancer cells.3.In prostate cancer cells,ZEB1 may also increase the resistance of prostate cancer cells to enzalutamide by inhibiting the expression of AR.