Fenofibrate down-regulates the expressions of androgen receptor (AR) and AR target genes and induces oxidative stress in the prostate cancer cell line LNCaP

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• 作者：Hu Zhao^a ; ¹ ; Chen Zhu^a ; ¹ ; Chao Qin^a ; ¹ ; Tao Tao^b ; Jie Li^a ; Gong Cheng^a ; Pu Li^a ; Qiang Cao^a ; Xiaoxin Meng^a ; Xiaobing Ju^a ; Pengfei Shao^a ; Lixin Hua^a ; Min Gu^a ; ^{medzhao1980@163.com} ; Changjun Yin^a ; ^{drcjyin@gmail.com}
• 关键词：Fenofibrate ; LNCaP ; Androgen receptor ; Oxidative stress
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2013
• 出版时间：8 March, 2013
• 年：2013
• 卷：432
• 期：2
• 页码：320-325
• 全文大小：718 K

文摘

Fenofibrate, a peroxisome proliferator-androgen receptor-alpha agonist, is widely used in treating different forms of hyperlipidemia and hypercholesterolemia. Recent reports have indicated that fenofibrate exerts anti-proliferative and pro-apoptotic properties. This study aims to investigate the effects of fenofibrate on the prostate cancer (PCa) cell line LNCaP. The effects of fenofibrate on LNCaP cells were evaluated by flow cytometry, reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assays, Western blot analysis, and dual-luciferase reporter assay. Fenofibrate induces cell cycle arrest in G1 phase and apoptosis in LNCaP cells, reduces the expressions of androgen receptor (AR) and AR target genes (prostate-specific antigen and TMPRSS2), and inhibits Akt phosphorylation. Fenofibrate can induce the accumulation of intracellular reactive oxygen species and malondialdehyde, and decrease the activities of total anti-oxidant and superoxide dismutase in LNCaP cells. Fenofibrate exerts an anti-proliferative property by inhibiting the expression of AR and induces apoptosis by causing oxidative stress. Therefore, our data suggest fenofibrate may have beneficial effects in fenofibrate users by preventing prostate cancer growth through inhibition of androgen activation and expression.