Targeted degradation of androgen receptors in androgen-independent prostate cancer cells: an experimental study.
- Author:
Yun-Feng SHI
1
;
Yue-Qing TANG
;
Xiao-Wen SUN
;
Dian-Jun YU
;
Bang-Min HAN
;
Yan HONG
;
Shu-Jie XIA
Author Information
- Publication Type:Journal Article
- MeSH: Antineoplastic Agents; pharmacology; Apoptosis; Cell Line, Tumor; Cell Proliferation; Humans; Male; Prostate-Specific Antigen; metabolism; Prostatic Neoplasms; drug therapy; metabolism; pathology; Receptors, Androgen; metabolism
- From: National Journal of Andrology 2009;15(12):1059-1063
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo 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.
METHODSC4-2B 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.
RESULTSCompared 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).
CONCLUSIONThe 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.
