ω3多不饱和脂肪酸代谢产物前列腺素E3(PGE3)和消退素(resolvins)抗前列腺癌机制的研究

项目名称： ω3多不饱和脂肪酸代谢产物前列腺素E3(PGE3)和消退素(resolvins)抗前列腺癌机制的研究

项目编号： No.31471128

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 生理学与整合生物学

项目作者： 陈永泉

作者单位： 江南大学

项目金额： 82万元

中文摘要： 根据流行病学观点，基因、环境和日常饮食的相互作用影响人体健康，但机制性数据尚且不足。慢性炎症被认为是诱发许多人类疾病包括癌症的重要因素之一。申请人在脂肪与健康领域几十年的研究发现膳食中ω6多不饱和脂肪酸（polyunsaturated fatty acids，PUFAs）在炎症和肿瘤中起促进作用而ω3 PUFAs则与之相反。鉴于ω3 PUFAs的某些代谢产物往往具有较其本身更强的抗炎及抗肿瘤能力。本课题将用前列腺癌为模型，研究ω3 PUFAs代谢产物前列腺素E3（prostaglandin E3，PGE3）及消退素（Resolvins）对慢性炎症与癌症的影响。研究内容围绕PGE3及Resolvins抑制肿瘤细胞生长的作用方式、量效关系和协同作用，并探讨其中的分子机制。本课题的研究目标是在分子水平了解ω3PUFA抗肿瘤效应的机制，进而为膳食-基因相互作用对人体健康的影响奠定一定理论基础。

中文关键词： 多不饱和脂肪酸；类二十烷酸；前列腺素E3；消退素；癌症

英文摘要： Chronic inflammation is considered as a major cause of many human diseases including cancer. In the past several decades, significant attention has been paid to the role of genetic mutations in cancer. From Chinese medicine perspective, the environment has a significant impact on human health, however there is a genuine lack of mechanistic supporting data. Recent studies suggest that chronic inflammation and mutation may be mutually reinforcing processes that, left unchecked, can transform normal cells into potentially deadly cancer cells. What fuels the chronic flame? We hypothesize that dietary ω6 polyunsaturated fatty acid (PUFA) plays a key role. In contrast, ω3 PUFA inhibits chronic inflammation and cancer. Based upon our preliminary study, ω3 PUFA can be metabolized by cyclooxygenase (COX) into eico/docosanoids, which have significant anti-inflammatory function. In this proposal, we will use prostate cancer as a model to study the role of PGE3 and Resolvins in chronic inflammation and cancer. Two specific aims are (1) study the dose and cooperative effect of PGE3 and Resolvin on tumor cells, (2) determine the mechanism by which PGE3 and Resolvin inhibit tumor cell proliferation. Our short-term goal is to understand the molecular mechanistic interplay between dietary fat, inflammation and cancer. Our long-term goal is to lay a foundation for future investigations on the role of environment-gene interaction in human health.

英文关键词： polyunsaturated fatty acid;eicosanoid;PGE3;resolvin;cancer