Effect And Mechanism Of Abiraterone Acetate On Chemosensitivity Of In Goserelin Castration-resistant Prostate Cancer PC3 Cells

Objective To investigate the effects of abiraterone acetate（AA）on chemotherapy sensitivity of goserelin castration-resistant prostate cancer（CRPC）PC3 cells and its mechanism.Methods MTT assays were used to detect the proliferation inhibition rate of PC3 cells on AA and docetaxel（DOC）.PC3 cells were divided into blank group,AA group,DOC group and DOC+AA group.The cells in AA group and combined treatment group were treated with 20% lethal concentration（IC20）of abiraterone acetate,and the cells in DOC group and combined treatment group were treated with IC20 dose of Docetaxel,respectively.MTT assays were used to evaluate the proliferation inhibition rate of PC-3 cells in the above four groups at 24,48 and 72 hours.Flow cytometry was used to detect the apoptosis rate of each group at 48 hours.The protein levels of apoptosis related markers（Bcl-2,Bax,caspase 3）and drug resistance related markers（P-glycoprotein and Mcl-1）were detected by Western blot.Results（1）IC20 values of PC3 cells for AA and DOC were 2.20 nmol/L and 7.52 nmol/L,respectively.（2）Compared with the control group,the absorbance values of PC-3 cells in AA group,Doc group and combined treatment group decreased significantly at 48 and 72 hours,and the absorbance values of combined treatment group were significantly lower than those in AA group and DOC group.（3）Apoptosis rates of control group,AA group,Doc group and DOC + AA group were（5.81 ± 1.30）%,（14.71 ± 2.66）%,（15.35 ± 2.60）% and（24.61 ± 3.50）%,respectively.Compared with the control group,apoptosis rate of all drug treatment groups were significantly elevated.In addition,the apoptosis rate of the combined treatment group was significantly higher than those in the AA group and DOC group.（4）As the results of Western blot showed,the protein level of Bcl-2 were reduced in all drug treatment groups,especially in the combined treatment group.By contrast,levels of Bax and Caspase3 protein levesl were up-regulated in all drug treatment groups.（5）Compared with the control group,protein levels of P-gp and Mcl-1 were decreased in all drug treatment groups,and the decrease in the combined treatment group was more significant.Conclusion Abiraterone acetate can effectively inhibit the proliferation and promote apoptosis of goserelin castration resistant prostate cancer PC3 cells.Moreover,abiraterone acetate increases the sensitivity of PC-3 cells to chemotherapy,which may be related to its regulation action for expression of apoptosis and drug resistance related proteins.