The study of CUDC-101 inhibits the expression of AR-V7 in castration-resistant prostate cancer cells / 中华泌尿外科杂志

ABSTRACT

Objective To solve the problem of castration resistant prostate cancer (castrationresistant prostate cancer,CRPC) the problem of drug resistance by studing the expression of the CUDC-101 inhibitor of castration resistant prostate cancer androgen receptor splice variant 7.Methods In this study,the expression of AR-V7 protein in prostate cancer cell lines PC-3,VCaP,22Rv1,LNCap was detected by imnmunoblotting between April 2015 and April 2016,and the highest expression level of cell lines was selected follow-up experiments.Through the cell proliferation and activity experiments,the epigenetic inhibitorshistone deacetylase inhibitor CUDC-101,histone methylation inhibitor DZNeP,DNA methylation inhibitor gemcitabine,histone acetyltransferase inhibitor MG149 to select an inhibitor that reduces the expression of AR-V7 protein in CRPC cells.22Rv1 cells were treated with 30 nmol and 300 nmol of CUDC101 and 1,10 and 20 μmol of Enzalutamide (MDV3100),respectively,and their inhibitory effects on the growth of 22Rv1 cells were examined.Results The results of immunoblotting showed that AR-V7 protein was only expressed in CRPC cell line 22Rv1 and negative in non-CRPC cell line.The expression of AR-V7 in 22Rv1 cells treated with CUDC-101 was significantly lower than that of negative control.While other inhibitors had no effect on the expression of AR-V7.In the cell proliferation and activity assay,the inhibitory rates of 30 nmol CUDC-101 and 1,10 and 20 μmol MDV3100 were 10％,35％ and 45％,respectively,higher than that of MDV3100 alone.28％ and 42％,the difference was statistically significant (P ＜ 0.05).The inhibitory rates of 300 nmol CUDC-101 and MDV3100 were 30％,60％ and 65％,respectively,which were significantly higher than those of MDV3100 alone (P ＜ 0.05).Conclusions CUDC-101 can inhibit the castration resistant prostate cancer androgen receptor splice variant 7 expression,and solved the resistance problem of CRPC.