Mechanism of Fish Oil Supplements in Prevention of Cance

描述（由申请人提供）：该计划项目资助申请涉及来自维克森林大学的一组研究人员，以了解n- 3fa的作用机制，特别是那些在鱼油补充剂中发现的与前列腺癌有关的作用机制。我们试图解决以下问题：n-3脂肪酸在减少前列腺癌发病率、进展和转移方面的效率如何？早期、晚期或终生摄入n-3脂肪酸对前列腺癌进展有不同影响吗？n-6脂肪酸代谢酶抑制剂对前列腺癌是否有与鱼油相似的有益效果？最后但并非最不重要的是，鱼油抑制前列腺癌进展的分子机制是什么？我们提出了一套四个整合互补的研究项目和三个核心。它们旨在从不同的角度解决复杂的问题，每个项目的结果将有助于改进其他项目。我们充分利用我们在体内和体外模型系统方面的优势。首次全面、系统地分析了鱼油饮食对前列腺组织的相关分子变化（mRNA和脂质）。此外，还将采用常规的途径解剖方法（项目I为磷酸肌肽途径，项目II为类生态酸途径，项目III为血小板活化因子途径，项目IV为syndecan途径）来研究鱼油对前列腺癌的作用机制。

DESCRIPTION (provided by applicant): This Program Project Grant application involves a group of investigators from Wake Forest University to understand the mechanism of action for n-3 FA, particularly those found in fish oil supplements, as relate to prostate cancer. We attempt to address the following questions: How efficient is n-3 fatty acids in reducing prostate cancer incidence, progression and metastasis in a genetically defined, immune-competent animal model with orthotopic prostate cancer? Will n-3 fatty acid intake at early age, later age or life-long have different effects on prostate cancer progression? Do inhibitors of n-6 fatty acid metabolizing enzymes have similar beneficial effect for prostate cancers as fish oil? Last but not least, what is (are) the molecular mechanism(s) by which fish oil suppress prostate cancer progression? We propose a set of four integrated and complementary research projects and three cores. They are designed to tackle a complex problem from various angles, and results from each project will help to refine others. We take advantage of our strengths of in vivo and in vitro model systems. For the first time, molecular changes (mRNA and lipid) associated with fish oil diet in the prostate will be comprehensively and systematically analyzed. In addition, conventional pathway dissection approach (phosphoinositide pathway in Project I, ecosanoid pathway in Project II, platelet activating factor pathway in Project III and syndecan pathway in Project IV) will also be applied to study the mechanism of action of fish oil on prostate cancer.