增殖抑制基因（HSG）协同顺铂促进人肺腺癌细胞线粒体途径凋亡的机制研究

项目名称： 增殖抑制基因（HSG）协同顺铂促进人肺腺癌细胞线粒体途径凋亡的机制研究

项目编号： No.81201839

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学2

项目作者： 楼煜清

作者单位： 上海交通大学

项目金额： 23万元

中文摘要： 晚期肺腺癌主要以铂类为基础的联合化疗方案治疗，但缺乏疗效预测基因。本课题组前期研究发现，增殖抑制基因（HSG）可通过MAPK信号传导通路诱导细胞线粒体途径凋亡，与顺铂诱导肿瘤细胞凋亡有相同的信号传导通路，两者可能有协同性。本课题拟通过细胞水平和整体动物水平研究，根据线粒体途径凋亡调控基因p53表达情况及调控药物ABT-737耐药情况不同，选取A549、Calu-6、NCI-H1299三种人肺腺癌细胞株，运用腺病毒转染技术分别建立HSG高表达细胞株。在细胞水平层面，在顺铂、ABT-737干预与否的体系中，分析HSG表达程度不同细胞株凋亡率及凋亡基因和蛋白表达的差异；在整体动物层面，建立裸鼠瘤荷模型，比较HSG表达程度不同细胞株在顺铂、ABT-737干预与否时的成瘤情况、凋亡基因和蛋白表达的差异，探讨HSG基因协同顺铂促进人肺腺癌细胞线粒体途径凋亡机制及p53基因、ABT-737对其调控作用。

中文关键词： 增殖抑制基因；肺肿瘤；细胞凋亡；顺铂；

英文摘要： Platinum-based chemotherapy is the first-line treatment in advanced lung adenocarcinoma. Unfortunately, the research on profiling of genes expression in predicting the efficacy of this treatment has not got exciting results. Our previous study suggested that hyperplasia suppressor gene (HSG) induced apoptosis of mitochondrial pathway via MAPK signal transduction pathway, which had the similar pathway on tumor cell apoptosis induced by cisplatin. So we supposed that it might be in synergistic effects in apoptosis mechanisms with HSG and cisplatin. The current study would be performed in vitro and in vivo. Three human lung adenocarcinoma cell lines, A549, Calu-6 and NCI-H1299, were chosen according to two factors, the expression of p53, an important regulator in mitochondrial pathway of apoptosis, and drug resistance to another regulator, ABT-737. Adenoviral-mediated gene transfer would be performed to make human HSG overexpression in the cell lines. In vitro, the apoptotic rate of the cell lines and the expression of the apoptosis-related genes and proteins would be analyzed in relation to the degrees of differential HSG expression and the effects of cisplatin and ABT-737. In vivo, tumor models in nude mice would be generated. Tumor formation and progression in these mice and the expression of the apoptosis-relat

英文关键词： hyperplasia suppressor gene；lung neoplasms；apoptosis；cisplatin；