Clostridium scindens metabolites trigger prostate cancer progression through androgen receptor signaling

被引：16

作者：

Bui, Ngoc-Niem ^{[1
,2
]}

Li, Chen-Yi ^{[1
]}

Wang, Ling-Yu ^{[1
]}

Chen, Yu-An ^{[3
,4
]}

Kao, Wei-Hsiang ^{[3
,4
]}

Chou, Li-Fang ^{[1
,5
]}

Hsieh, Jer-Tsong ^{[4
]}

Lin, Ho ^{[3
,6
,7
]}

Lai, Chih-Ho ^{[1
,8
,9
,10
,11
]}

机构：

[1] Chang Gung Univ, Grad Inst Biomed Sci, Dept Microbiol & Immunol, Dept Biochem, Taoyuan, Taiwan

[2] Can Tho Univ Med & Pharm, Fac Med, Can Tho, Vietnam

[3] Natl Chung Hsing Univ, Dept Life Sci, Taichung, Taiwan

[4] Univ Texas Southwestern Med Ctr, Dept Urol, Dallas, TX USA

[5] Chang Gung Mem Hosp, Kidney Res Ctr, Linkou, Taiwan

[6] Natl Chung Hsing Univ, Ph D Program Translat Med, Taichung, Taiwan

[7] Natl Chung Hsing Univ, Rong Hsing Res Ctr Translat Med, Taichung, Taiwan

[8] China Med Univ & Hosp, Sch Med, Dept Med Res, Taichung, Taiwan

[9] Asia Univ, Dept Nursing, Taichung, Taiwan

[10] Chang Gung Mem Hosp, Mol Infect Dis Res Ctr, Dept Pediat, Linkou, Taiwan

[11] Chang Gung Univ, Dept Microbiol & Immunol, Taoyuan, Taiwan

来源：

JOURNAL OF MICROBIOLOGY IMMUNOLOGY AND INFECTION | 2023年 / 56卷 / 02期

关键词：

Clostridium scindens; Bacterial metabolite; Prostate cancer; Androgen; BILE-SALT BIOTRANSFORMATIONS; 20-ALPHA-HYDROXYSTEROID DEHYDROGENASE; GLUCOCORTICOID-RECEPTOR; PHOSPHORYLATION; BIOSYNTHESIS; RESISTANCE; STEROIDS; TISSUE; CELLS;

D O I：

10.1016/j.jmii.2022.12.009

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Prostate cancer (PCa) is one of the most common malignancies in men; recently, PCa-related mortality has increased worldwide. Although androgen deprivation therapy (ADT) is the standard treatment for PCa, patients often develop aggressive castration-resistant PCa (CRPC), indicating the presence of an alternative source of androgen. Clos-tridium scindens is a member of the gut microbiota and can convert cortisol to 11b-hydroxyan-drostenedione (11b-OHA), which is a potent androgen precursor. However, the effect of C. scindens on PCa progression has not been determined. In this study, androgen-dependent PCa cells (LNCaP) were employed to investigate whether C. scindens-derived metabolites acti-vate androgen receptor (AR), which is a pivotal step in the development of PCa. Results showed that cortisol metabolites derived from C. scindens-conditioned medium promoted proliferation and enhanced migration of PCa cells. Furthermore, cells treated with these me-tabolites presented activated AR and stimulated AR-regulated genes. These findings reveal that C. scindens has the potential to promote PCa progression via the activation of AR signaling. Further studies on the gut-prostate axis may help unravel an alternative source of androgen that triggers CRPC exacerbation.Copyright 2023, Taiwan Society of Microbiology. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

引用

页码：246 / 256

页数：11