Zhao Heng, Pflug Beth R, Lai Xianyin, Wang Mu
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA.
Department of Medicine, Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, IN, USA.
Proteomics Clin Appl. 2016 Mar;10(3):267-79. doi: 10.1002/prca.201500066. Epub 2015 Dec 10.
The aim of this study is to investigate the role of n-3 and n-9 fatty acids in crucial processes involved in prostate cancer cell growth through a large-scale proteomic analysis.
We used a label-free protein quantification method to profile global protein expression of fish oil and oleic acid treated PCa cells and validated a panel of differentially expressed proteins by either Western blot or multiple reaction monitoring. Bioinformatic analysis was also performed to uncover the pathways involved in fatty acid metabolism.
Fish oil, not oleic acid, suppresses prostate cancer cell viability. Assessment of fatty acid synthesis pathway activity also shows that oleic acid is a more potent inhibitor than fish oil on de novo fatty acid synthesis. Although fatty acid synthase activity decreases with fish oil treatment, the inhibition of its activity occurs over time while reduction in viability occurs within 24 h. Bioinformatic analysis revealed the pathways altered by these fatty acid treatments.
This study suggests that suppression of cell viability by fish oil is independent of fatty acid synthase and fish oil regulates prostate cancer cells through activation of other pathways depending upon length of exposure to fish oil.
本研究旨在通过大规模蛋白质组学分析，探讨n-3和n-9脂肪酸在前列腺癌细胞生长关键过程中的作用。
我们采用无标记蛋白质定量方法，分析鱼油和油酸处理的前列腺癌细胞的整体蛋白质表达谱，并通过蛋白质免疫印迹法或多反应监测验证一组差异表达蛋白质。还进行了生物信息学分析，以揭示脂肪酸代谢相关途径。
鱼油而非油酸可抑制前列腺癌细胞活力。脂肪酸合成途径活性评估还表明，油酸在从头合成脂肪酸方面比鱼油是更强效的抑制剂。尽管鱼油处理会使脂肪酸合酶活性降低，但其活性抑制随时间发生，而细胞活力在24小时内就会下降。生物信息学分析揭示了这些脂肪酸处理所改变的途径。
本研究表明，鱼油对细胞活力的抑制与脂肪酸合酶无关，且鱼油根据暴露时间长短通过激活其他途径来调节前列腺癌细胞。
