title: [Targeted degradation of androgen receptors in androgen-independent prostate cancer cells: an experimental study].
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
  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.
authors.affiliation: Department of Urology, The First People's Hospital Afiliated to Shanghai Jiaotong University, Shanghai 200080, China.
authors.forename: Yun-Feng
authors.initials: YF
authors.lastname: Shi
authors.forename: Yue-Qing
authors.initials: YQ
authors.lastname: Tang
authors.forename: Xiao-Wen
authors.initials: XW
authors.lastname: Sun
authors.forename: Dian-Jun
authors.initials: DJ
authors.lastname: Yu
authors.forename: Bang-Min
authors.initials: BM
authors.lastname: Han
authors.forename: Yan
authors.initials: Y
authors.lastname: Hong
authors.forename: Shu-Jie
authors.initials: SJ
authors.lastname: Xia
mesh_terms: 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*
chemical_list: C410798:AR protein, human; D000970:Antineoplastic Agents; D011944:Receptors, Androgen; D017430:Prostate-Specific Antigen