Fujimoto Naohiro
   Department   School of Medicine  Urology, Clinical Medical Sciences
Article types journal article
Language English
Peer review Peer reviewed
Title Mineralocorticoid receptor signaling affects therapeutic effect of enzalutamide.
Journal Formal name:The Prostate
ISSN code:10970045/02704137
Domestic / ForeginForegin
Volume, Issue, Page 78(14),1045-1052頁
Author and coauthor Shiota Masaki, Fujimoto Naohiro, Higashijima Katuyoshi, Imada Kenjiro, Kashiwagi Eiji, Takeuchi Ario, Inokuchi Junichi, Tatsugami Katsunori, Kajioka Shunichi, Uchiumi Takeshi, Eto Masatoshi
Publication date 2018/05
Summary BACKGROUND:Corticosteroids play important roles in prostate cancer therapeutics. However, their role when combined with enzalutamide remains obscure. Then, we aimed to elucidate the functional and clinical impact of corticosteroids on steroid receptors in androgen receptor (AR)-targeting therapy utilizing enzalutamide.METHODS:The therapeutic effect was studied according to concomitant use of corticosteroids in 86 men treated with enzalutamide. The sensitivity to various agents was evaluated using cytotoxicity assays in prostate cancer cells. Gene expression levels were evaluated by quantitative real-time polymerase chain reaction in prostate cancer cells and tissues.RESULTS:The therapeutic effect of enzalutamide was particularly lessened with concomitant treatment with dexamethasone. Consistently, dexamethasone increased cellular resistance to enzalutamide while prednisolone and aldosterone decreased cellular resistance to enzalutamide in prostate cancer cells. Inversely, mineralocorticoid receptor (MR) knockdown augmented the activity of AR signaling and the cellular resistance to enzalutamide.CONCLUSIONS:MR plays a critical role in resistance to AR-targeting therapies, which may be overcome by activation of MR signaling.
DOI 10.1002/pros.23661
PMID 29851126