Development of antiandrogen-resistance in advanced prostate cancer involves multiple androgen receptor (AR)-dependent and -independent pathways.
Here, we demonstrated that endothelial nitric oxide synthase (eNOS) exhibited an overexpression pattern in hormone-refractory prostate cancer and several models of advanced hormone-resistant prostate cancer. We further established a novel in vitro model of antiandrogen-resistant prostate cancer (LNCaP-BC) by long-term bicalutamide treatment. Besides antiandrogen-resistant and other enhanced malignant growth phenotypes, LNCaP-BC cells exhibited an increased activated eNOS expression and NO production, and suppressed AR transactivation status. Treatment with a NOS inhibitor L-NAME could re-sensitize the growth response to bicalutamide and enhance the AR transactivation in LNCaP-BC cells. Together, our present findings indicate that increased NO production by acquired increased expression of activated eNOS could contribute to the antiandrogen-resistant growth of prostate cancer cells, via a mechanism of NO-mediated suppression of AR activity, and also targeting eNOS could be a potential therapeutic strategy for antiandrogen-resistant prostate cancer.
Copyright © 2012. Published by Elsevier Ireland Ltd.
Written by:
Yu S, Jia L, Zhang Y, Wu D, Xu Z, Ng CF, To KK, Huang Y, Chan FL Are you the author?
School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China
Reference: Cancer Lett. 2012 Sep 18. pii: S0304-3835(12)00543-5
doi: 10.1016/j.canlet.2012.09.006
PubMed Abstract
PMID: 22995070
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