[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).

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.

• Authors: Yun-Feng Shi, Yue-Qing Tang, Xiao-Wen Sun, Dian-Jun Yu, Bang-Min Han, Yan Hong, Shu-Jie Xia
• Journal: Zhonghua nan ke xue = National journal of andrology (Zhonghua Nan Ke Xue) Vol. 15 Issue 12 Pg. 1059-63 (Dec 2009) ISSN: 1009-3591 [Print] China
• PMID: 20180412 (Publication Type: English Abstract, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• AR protein, human
• Antineoplastic Agents
• Receptors, Androgen
• Prostate-Specific Antigen

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis
• Cell Line, Tumor
• Cell Proliferation
• Humans
• Male
• Prostate-Specific Antigen (metabolism)
• Prostatic Neoplasms (drug therapy, metabolism, pathology)
• Receptors, Androgen (metabolism)