缺氧反应元件启动子增强Jab1基因表达联合长双歧杆菌对肺癌缺氧区癌细胞化疗敏感性调控的研究

项目名称： 缺氧反应元件启动子增强Jab1基因表达联合长双歧杆菌对肺癌缺氧区癌细胞化疗敏感性调控的研究

项目编号： No.30801366

项目类型： 青年科学基金项目

立项/批准年度： 2009

项目学科： 生物科学

项目作者： 胡明冬

作者单位： 中国人民解放军第三军医大学

项目金额： 18万元

中文摘要： 肺癌缺氧区癌细胞是化疗耐药产生和治疗失败的重要原因。研究表明：增强肺癌缺氧区癌细胞对化疗药物的敏感性是避免耐药产生的重要策略之一。但缺乏有效的基因治疗靶点以及目的基因不能在肺癌缺氧区高效表达是目前研究的最主要障碍。本课题利用专职调控肺癌细胞凋亡的基因Jab1，构建由缺氧反应元件启动子驱动的真核表达载体，并采用具有缺氧环境趋化性能的厌氧长双歧杆菌为基因载体，在缺氧及设置空白对照的条件下，通过利用阿霉素、顺铂等化疗药物，探讨Jab1 基因表达增强后在体内外对人肺腺癌A549 细胞化疗敏感性的调控作用。研究目的在于探讨厌氧长双歧杆菌介导的Jab1 基因表达对肺癌缺氧区癌细胞化疗敏感性的影响，希望找到对肺癌缺氧区癌细胞具有增敏效果的普适性调控手段，研究结果对克服肺癌化疗耐药和改善患者预后均具有积极的指导意义。

中文关键词： 肺癌；Jab1；化疗敏感性；凋亡；长双岐杆菌

英文摘要： Hypoxic zone cancer cell in lung cancer is one of the important reasons in chemotherapy drug resistance and treatment failure. Research indicated that enhancing sensitivity of the hypoxic zone lung cancer cells to chemotherapeutic drug is an important strategy to avoid the chemotherapy drug resistance. However, the lack of effective gene therapy and gene targets can not be highly expressed on the hypoxic zone cancer cells is the most important obstacles. Here we constructed Jab1 gene eukaryotic expression vector driven by hypoxia response element promoter and use the Bifidobacterium longum as vector transfer in hypoxic environment. Doxorubicin,cisplatin and other chemotherapy drugs were used to investigate the chemosensitivity of lung cancer cell A549 with or without Jab1 gene both in vivo and in vitro. This study is to explore the effects of bifidobacterium longum -mediated Jab1 gene expression in the hypoxic area of lung cancer on the chemotherapy sensitivity of cancer cells. The results will help to overcome drug resistance in lung cancer chemotherapy and improve the prognosis of patients in the future.

英文关键词： lung cancer; Jab1; chemotherapeutic sensitivity; apoptosis; Bifidobacterium longum