Targeted Degradation of Androgen Receptors in Androgen-Independent Prostate Cancer Cells:An Experimental Study
SHI Yun-feng
TANG Yue-qing
SUN Xiao-wen
YU Dian-jun
HAN Bang-min
HONG Yan
XIA Shu-jie
Abstract：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 CA-2B cells,and explore the proliferation,secretion and apoptosis of the treated cells.Methods:G4-2B cells were treated with DHT-PBOTAC,and then the expressions of the AR protein and caspase3 in the CA-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 CA-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 inhibito-ry 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 CA-2B cells.
Keywords：androgen receptorandrogen-independent prostate cancerproteolysischimeric molecule
Publication Date：2009-11-28
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：5( 1059-1063 )