[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 CA-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 MIT 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).


CONCLUSIONS
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.
Shi
Yun-Feng
YF
Department of Urology, The First People's Hospital Afiliated to Shanghai Jiaotong University, Shanghai 200080, China.
Tang
Yue-Qing
YQ
Sun
Xiao-Wen
XW
Yu
Dian-Jun
DJ
Han
Bang-Min
BM
Hong
Yan
Y
Xia
Shu-Jie
SJ
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D008297:Male; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D011944:Receptors, Androgen / Q000378:metabolism*
C410798:AR protein, human; D000970:Antineoplastic Agents; D011944:Receptors, Androgen; D017430:Prostate-Specific Antigen