Bordetella源性胆固醇氧化酶诱导肺腺癌细胞凋亡的机制研究

项目名称： Bordetella源性胆固醇氧化酶诱导肺腺癌细胞凋亡的机制研究

项目编号： No.81201778

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1

项目作者： 林彦良

作者单位： 山东大学

项目金额： 23万元

中文摘要： 近期研究结果表明，膜胆固醇的清除能够诱导肿瘤细胞凋亡，为肿瘤治疗提供了新的靶点。我们首次将能够氧化胆固醇的胆固醇氧化酶（COD-B）应用到肿瘤治疗领域，结果显示，COD-B与肺癌细胞A549共孵育（胞外作用）及COD-B基因导入（胞内作用）均能够诱导A549凋亡，且添加外源胆固醇促进了A549的凋亡，其机制尚不清楚。本项目拟通过COD-B与肺腺癌细胞共孵育及COD-B基因导入肺腺癌细胞两种方式，分别在血清饥饿或高胆固醇条件下，研究COD-B对肺腺癌细胞的影响，明确膜胆固醇及外源胆固醇氧化在诱导细胞凋亡中的作用机制，确定COD-B诱导肺腺癌细胞凋亡的机理，具有重要的理论意义及应用价值；通过病毒介导COD-B基因在肿瘤动物模型中表达，确定COD-B的酶学性质对其在肿瘤及正常组织中选择性作用的影响，探讨COD-B作为肿瘤靶向药物的可能性，同时从酶学角度为肿瘤杀伤蛋白的筛选提供一定的理论依据。

中文关键词： 胆固醇；胆固醇氧化酶；肺腺癌；凋亡；转移

英文摘要： Recent researchs have demonstrated that depletion of membrane cholesterol could induce apoptosis of tumor cells, which provided novel target for tumor therapy.Cholesterol oxidase (COD-B),an enzyme catalysing oxidation of cholesterol,was first applied in the field of tumor therapy. The results suggested that COD-B could induce apoptosis of human lung cancer A549 cells when it was incubated directly with A549.Expression of COD-B gene in A549 could also inhibit the growth of A549, and the inhibition effect of COD-B on A549 was enhanced by addition of cholesterol，which was opposite to previous reports.The functional mechanism of COD-B was unclear.In this project,the influence of COD-B on lung adenocarcinoma cells cultured in serum-starved or cholesterol-rich medium would be brought to light by incubating COD-B with cells and expression of COD-B in lung adenocarcinoma cells, which was beneficail to confirm the mechanism of apoptosis of lung adenocarcinoma cells induced by oxidation of membrane cholesterol and exogenous cholesterol.The mechanism of apoptosis of lung adenocarcinoma cells induced by COD-B would be revealed clearly,which possessed great theoretical significance and application value.By the virus-mediated expression of COD-B gene in animal model of tumor,the effect of COD-B enzymatic properties on the se

英文关键词： cholesterol；cholesterol oxidase；lung adenocarcinoma；apoptosis；metastasis