γ-Oryzanol Reduces Caveolin-1 and PCGEM1 Expression, Markers of Aggressiveness in Prostate Cancer Cell Lines
γ-Oryzanol Reduces Caveolin-1 and PCGEM1 Expression, Markers of Aggressiveness in Prostate Cancer Cell Lines
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DOI：
10.1002/pros.22960
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发表时间：
2015-06-01
期刊：
影响因子：
2.8
通讯作者：
Guma, Fatima T. C. R.
中科院分区：
文献类型：
--
作者：
Hirsch, Gabriela E.;Parisi, Mariana M.;Guma, Fatima T. C. R.
前列腺癌是男性死亡的主要原因，因为晚期疾病的治疗策略有限。- 谷维素是米糠的一种成分，富含植物甾醇，以其抗氧化、抗癌和内分泌作用而闻名。已知谷维素可通过下调抗氧化基因影响前列腺癌细胞，植物甾醇具有抗增殖和凋亡作用。有证据表明，谷维素的一些成分可以调节基因参与前列腺癌的发生和发展，如小窝蛋白-1（Cav-1）和前列腺特异性雄激素调节基因（PCGEM 1）。方法为了确定谷维素对前列腺癌细胞存活的影响，我们分别通过MTT法和磺酰罗丹明B法来评估细胞活力和生物量。流式细胞仪检测细胞死亡、细胞周期和pERK 1/2活性。通过真实的时间逆转录聚合酶链反应（RT-PCR）和免疫荧光以及共聚焦显微镜分析来评估前列腺癌cav-1和PCGEM 1基因表达的变化以及cav-1蛋白的变化。（PC 3和DU 145）和响应性（LNCaP）细胞系，以及在LNCaP和DU 145细胞中通过pERK 1/2的信号传导。- 谷维素还似乎在PC 3和LNCaP细胞中阻断G2/M的细胞周期进展，在DU 145细胞中阻断G 0/G1的细胞周期进展。这些影响伴随着下调cav-1的表达在雄激素无反应细胞系和PCGEM 1基因在DU 145和LNCaP celles. CONCLUSION总之，我们用生物化学和遗传学的方法来证明，谷维素显示一个有前途的辅助作用，在前列腺癌的治疗。前列腺75：783-797，2015年。(c)2015 Wiley Periodicals，Inc.
BACKGROUNDProstate cancer is a leading cause of death among men due to the limited number of treatment strategies available for advanced disease. -oryzanol is a component of rice bran, rich in phytosterols, known for its antioxidant, anti-carcinogenic and endocrinological effects. It is known that -oryzanol may affect prostate cancer cells through the down regulation of the antioxidant genes and that phytosterols have anti-proliferative and apoptotic effects. There are evidences showing that some of the components of -oryzanol can modulate genes involved in the development and progression of prostate cancer, as caveolin-1 (Cav-1) and prostate specific androgen-regulated gene (PCGEM1).METHODSTo determine the effects of -oryzanol on prostate cancer cell survival we evaluated the cell viability and biomass by MTT and sulforhodamine B assays, respectively. Cell death, cell cycle and pERK1/2 activity were assessed by flow cytometry. The changes in gene expression involved in the survival and progression of prostate cancer cav-1 and PCGEM1 genes were evaluated by quantitative real time reverse transcriptase polymerase chain reaction (RT-PCR) and cav-1 protein by immunofluorescence followed by confocal microscopy analysis.RESULTSWe found that -oryzanol decreases cell viability and culture biomass by apoptosis and/or necrosis death in androgen unresponsive (PC3 and DU145) and responsive (LNCaP) cell lines, and signals through pERK1/2 in LNCaP and DU145 cells. -oryzanol also appears to block cell cycle progression at the G2/M in PC3 and LNCaP cells and at G0/G1 in DU145 cells. These effects were accompanied by a down regulation in the expression of the cav-1 in both androgen unresponsive cell lines and PCGEM1 gene in DU145 and LNCaP cells.CONCLUSIONIn summary, we used biochemical and genetics approaches to demonstrate that -oryzanol show a promising adjuvant role in the treatment of prostate cancer. Prostate 75:783-797, 2015. (c) 2015 Wiley Periodicals, Inc.