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

机译:非诺贝特下调前列腺癌细胞系LNCaP中雄激素受体(AR)和AR靶基因的表达并诱导氧化应激

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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. ? 2013 Elsevier Inc.
机译:非诺贝特是一种过氧化物酶体增殖物-雄激素受体-α激动剂,被广泛用于治疗不同形式的高脂血症和高胆固醇血症。最近的报道表明非诺贝特具有抗增殖和促凋亡的作用。这项研究旨在研究非诺贝特对前列腺癌(PCa)细胞LNCaP的影响。非诺贝特对LNCaP细胞的影响通过流式细胞仪,逆转录聚合酶链反应,酶联免疫吸附测定,蛋白质印迹分析和双荧光素酶报告基因测定进行评估。非诺贝特诱导LNCaP细胞的G1期细胞周期停滞和凋亡,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。非诺贝特可以诱导细胞内活性氧和丙二醛的积累,并降低LNCaP细胞中总抗氧化剂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凋亡。因此,我们的数据表明非诺贝特可能通过抑制雄激素的激活和表达来预防前列腺癌的生长,从而对非诺贝特使用者产生有益的作用。 ? 2013爱思唯尔公司

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