愈创醇增强NK细胞抗肺癌效应及抑制非小细胞肺癌细胞生长的作用与分子机制

项目名称： 愈创醇增强NK细胞抗肺癌效应及抑制非小细胞肺癌细胞生长的作用与分子机制

项目编号： No.81473237

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 朱诗国

作者单位： 上海中医药大学

项目金额： 67万元

中文摘要： 自然杀伤细胞（NK细胞）在恶性肿瘤免疫监视过程中发挥重要作用，而肿瘤细胞却能有效逃避包括NK细胞在内的免疫效应细胞的识别与杀伤。通过提高NK细胞对肿瘤细胞的识别与杀伤而阻断肿瘤细胞逃避NK细胞免疫监视已成为抗肿瘤药物发展的一个重要新方向。在前期研究中，通过对480种天然小分子化合物进行筛选和分析，我们发现倍半萜类化合物愈创醇既能够增强NK细胞对非小细胞肺癌（NSCLC）细胞的识别与杀伤，同时也能够直接抑制NSCLC细胞生长，是一种有效的新型抗肿瘤药物。本项目将围绕愈创醇增强NK细胞的抗肺癌效应与抑制NSCLC细胞生长两方面的作用，综合运用免疫共沉淀、流式细胞分析、蛋白芯片等现代分子生物学、免疫学和蛋白质组学等技术方法，深入探讨其抗NSCLC的作用、作用靶点和分子信号通路，阐明其抗NSCLC药理作用，为愈创醇作为抗肿瘤新药的研发提供理论基础和实验依据，亦为抗肿瘤药物的发展提供一种新的思路。

中文关键词： 愈创醇；非小细胞肺癌；抗肿瘤；自然杀伤细胞；分子机制

英文摘要： Natural Killer (NK) cell plays an important role in the tumor immunosurveillance,however,tumor cell can efficiently escape from immune effector cells including NK cells. Improving NK cell-mediated recognition and killing of cancer cells to block cancer immune evasion has become into an important novel strategy for the development of antitumor drugs.In previous study, through a large scale of screening of 480 natural products, we found that the sesquiterpenoid guaiol could not only enhance NK cell-mediated recognition and killing of non-small cell lung cancer (NSCLC) cells, but also could directly inhibit NSCLC cell growth. This discovery suggested guaiol might be a potent novel antitumor drug.In this project, we will be focused on guaiol-induced enhancement of NK cell-mediated lysis of lung cancer and inhibition of NSCLC cell growth, and deeply investigate its anti-NSCLC therapeutical efficacy, molecular targets and molecular signal pathaway to elucidate the anti-NSCLC pharmacological effects by comprehensive using molecular biological,immunological and proteomic technologies and methods, such as co-immunoprecipitation, flow cytometry analysis, proteinum chip,and so on. This study will provide theoretical support and experimental evidence for the research and development of guaiol as a novel antitumor drug, and also provide a new strategy for the devolepment of antitumor drugs.

英文关键词： Guaiol;NSCLC;Antitumor;NK cells;molecular mechanism