山核桃仁甾醇阿魏酸酯抑制肿瘤细胞效应及基于生物学通路的机理研究

项目名称： 山核桃仁甾醇阿魏酸酯抑制肿瘤细胞效应及基于生物学通路的机理研究

项目编号： No.31271847

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 农业科学

项目作者： 陆柏益

作者单位： 浙江大学

项目金额： 85万元

中文摘要： 前列腺癌是男性常见恶性肿瘤，发病率在我国逐年上升。甾醇阿魏酸酯结构特异，其比游离甾醇和阿魏酸具有更显著的抗炎、抗癌等功效。申请人前期研究发现山核桃仁中含有丰富的甾醇阿魏酸酯，且山核桃仁总甾醇提取物能显著抑制前列腺癌细胞（DU145）的增殖，但甾醇阿魏酸酯抗前列腺癌功效及作用机理尚无人研究。本项目以浙江、大别山、云南、湖南、贵州和美国等6种代表性山核桃仁为试材，结合植物化学、色谱化学、药理学和分子生物学等研究方法，分析山核桃仁甾醇阿魏酸酯组分及其品种差异和加工贮藏的影响，研究山核桃仁甾醇阿魏酸酯部位抗前列腺癌功效及其品种差异和加工贮藏的影响，阐明主要甾醇阿魏酸酯组分的生物效价，利用RT-PCR基因芯片、Western bloting等技术从基因和蛋白水平上揭示其抗前列腺癌的生物学通路和作用机理。本研究不仅为山核桃健康食用和深加工利用奠定科学基础，也为前列腺癌的防治提供新的思路。

中文关键词： 山核桃；甾醇阿魏酸酯；抑制肿瘤细胞增殖；信号通路；乳腺癌

英文摘要： Prostate cancer is one of the most prevalent urologic cancers in male. Steryl ferulate is a chemical structural combination of a plant sterol and an antioxidative ferulic acid, which is demonstrated to have more excellent bioactivity than free sterols and ferulic acid, such as anticancer and antiinflammatory. Pilot studies have shown that there are abundant of steryl ferulates in pecan, and the phytosterol-rich extract from pecan could inhibit significantly proliferation of DU145 cells, however, the studies on effects and its mechanism of steryl ferulate on anti-prostate cancer activity have not been done. Using six varieties of pecan (Zhejiang, Dabieshan, Yunnan, Hunan, Guizhou and America), the project is to analyze the effects of genetic variability, store and process on the steryl ferulate composition in the pecan by UPLC-MS/MS; determine the anti-prostate cancer activity and the steryl ferulate activity variance in all pecan samples on the perspective of genetic variability, store and process; evaluate the bioavailability of different steryl ferulates on anti-prostate cancer and identify dominated bio-active components combined by pharmacokinetics method; then elucidate the mechanism on biological pathway using real-time PCR array and Western bloting. In conclusion, our study would establish the basic unde

英文关键词： Pecan；Steryl ferulate；Pathway；Creast cancer；