Mineralocorticoid receptor signaling affects therapeutic effect of enzalutamide

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1045-1052
Number of pages8
JournalProstate
Volume78
Issue number14
DOIs
Publication statusPublished - Oct 1 2018

Fingerprint

Mineralocorticoid Receptors
Therapeutic Uses
Prostatic Neoplasms
Androgen Receptors
Adrenal Cortex Hormones
Dexamethasone
Steroid Receptors
Therapeutics
Prednisolone
MDV 3100
Aldosterone
Real-Time Polymerase Chain Reaction
Gene Expression

All Science Journal Classification (ASJC) codes

  • Oncology
  • Urology

Cite this

@article{95ddb653e3524289a361072b8f1da64b,
title = "Mineralocorticoid receptor signaling affects therapeutic effect of enzalutamide",
abstract = "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.",
author = "masaki shiota and Naohiro Fujimoto and Katuyoshi Higashijima and Kenjiro Imada and Eiji Kashiwagi and ario takeuchi and Junichi Inokuchi and Katsunori Tatsugami and Shunichi Kajioka and Takeshi Uchiumi and Masatoshi Eto",
year = "2018",
month = "10",
day = "1",
doi = "10.1002/pros.23661",
language = "English",
volume = "78",
pages = "1045--1052",
journal = "Prostate",
issn = "0270-4137",
publisher = "Wiley-Liss Inc.",
number = "14",

}

TY - JOUR

T1 - Mineralocorticoid receptor signaling affects therapeutic effect of enzalutamide

AU - shiota, masaki

AU - Fujimoto, Naohiro

AU - Higashijima, Katuyoshi

AU - Imada, Kenjiro

AU - Kashiwagi, Eiji

AU - takeuchi, ario

AU - Inokuchi, Junichi

AU - Tatsugami, Katsunori

AU - Kajioka, Shunichi

AU - Uchiumi, Takeshi

AU - Eto, Masatoshi

PY - 2018/10/1

Y1 - 2018/10/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85047802270&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85047802270&partnerID=8YFLogxK

U2 - 10.1002/pros.23661

DO - 10.1002/pros.23661

M3 - Article

AN - SCOPUS:85047802270

VL - 78

SP - 1045

EP - 1052

JO - Prostate

JF - Prostate

SN - 0270-4137

IS - 14

ER -