[Targeted degradation of androgen receptors in androgen-independent prostate cancer cells: an experimental study].

Objective:To investigate targeted degradation of the androgen receptor(AR)by chimeric molecules(DHT-PROTAC)via the ubiquitin-proteasome pathway in androgen-independent prostate cancer C4-2B cells,and explore the proliferation,secretion and apoptosis of the treated cells.Methods:C4-2B cells were treated with DHT-PROTAC,and then the expressions of the AR protein and caspase3 in the C4-2B cells were detected by immunohistochemistry and Western blot.The concentration of PSA in the supernatant was examined by ELISA.The cells were counted and their proliferation analyzed by a growth curve.The inhibitory effect on the growth of C4-2B cells was evaluated by MTT assay.Results:Compared with the control group,the DHT-PROTAC-treated group showed an obviously decreased expression of AR proteins with a significant attenuation of the band signals(P 0.05),a 40% reduction of the AR-positive cells and a 60% decrease of the PSA concentration in the supernatant(P 0.05).DHT-PROTAC exhibited an inhibitory effect on the C4-2B cells in a time-dependant manner(P 0.05).Conclusion:The chimeric molecule(DHT-PROTAC)can target the degradation of androgen receptors,reduce the secretion of PSA and repress the in vitro growth of C4-2B cells.