State Key Laboratory of Reproductive Medicine, Department of Urology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Biochem Biophys Res Commun. 2013 Mar 8;432(2):320-5. doi: 10.1016/j.bbrc.2013.01.105. Epub 2013 Feb 8.
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.
非诺贝特，一种过氧化物酶体增殖物激活受体-α激动剂，广泛用于治疗各种形式的高脂血症和高胆固醇血症。最近的报告表明，非诺贝特具有抗增殖和促凋亡作用。本研究旨在探讨非诺贝特对前列腺癌细胞系 LNCaP 的影响。通过流式细胞术、逆转录聚合酶链反应、酶联免疫吸附试验、Western blot 分析和双荧光素酶报告基因检测评估非诺贝特对 LNCaP 细胞的影响。非诺贝特诱导 LNCaP 细胞的细胞周期停滞在 G1 期并诱导细胞凋亡，降低雄激素受体 (AR) 和 AR 靶基因 (前列腺特异性抗原和 TMPRSS2) 的表达，并抑制 Akt 磷酸化。非诺贝特可诱导细胞内活性氧和丙二醛的积累，并降低 LNCaP 细胞中总抗氧化和超氧化物歧化酶的活性。非诺贝特通过抑制 AR 的表达发挥抗增殖作用，并通过引起氧化应激诱导细胞凋亡。因此，我们的数据表明，非诺贝特可能通过抑制雄激素激活和表达来预防前列腺癌的生长，对非诺贝特使用者具有有益的影响。
