JAB1过表达增加人肺腺癌细胞对化疗的敏感性  

Enhancement of human lung cancer cell sensitivity to chemotherapy by JAB1 over-expression

作　　者：胡明冬[1] 周长喜[2] 杨昱[1] 徐剑铖[1] 李琦[1] 

机构地区：[1]第三军医大学新桥医院呼吸内科研究所,重庆400037 [2]解放军总医院南楼呼吸内科,北京100853

出　　处：《局解手术学杂志》2011年第2期145-148,共4页Journal of Regional Anatomy and Operative Surgery

基　　金：国家自然科学基金资助项目(30801366)

摘　　要：目的通过探讨缺氧诱导因子1(HRE-1)启动子诱导JAB1过表达致人肺腺癌细胞(A549)对化疗敏感性的增加程度,来找到提高肺癌缺氧区肿瘤细胞对化疗敏感性的方法,最终达到逆转肺癌化疗耐药的目的。方法首先成功构建缺氧反应元件启动子所驱动的pUC57-HRE-JAB1真核表达质粒。随后,将该质粒导入A549细胞,化疗药物顺铂(C-DDP)也同时加入处理A549细胞。采用RFPCR和Western blot分别检测转染后A549中JAB1的mRNA和蛋白表达水平。采用流式细胞术检测经pUC57-HRE-JAB1质粒转染后A549细胞周期和凋亡的改变。结果较空白对照组和空载体组,经pUC57-HRE-JAB1真核表达质粒转染后,A549细胞中JAB1的表达明显增加(P<0.05)。同时,细胞周期被阻滞于G1期,并且转染后顺铂所诱导的细胞凋亡率较单纯顺铂处理明显增加(P<0.01)。更为重要的是,pUC57-HRE-JAB1导入增加了A549细胞对C-DDP的敏感性。结论缺氧诱导因子1启动子所诱导的JAB1过表达增加了肺癌细胞的化疗敏感性,为逆转肺癌化疗耐药提供了一种可行的治疗策略。Objective To search for the methods to increase the sensitivity of tumor cells to chemotherapy in anoxic zone of lung cancer and finally to reverse chemotherapeutic resistance of lung cancer by discussing the increasing of sensitivity of human lung cancer cell（A549） to chemotherapy through over-expression of JAB1 induced by hypoxia-inducible factor 1（HRE-1） promoter.Methods An eukaryotic expression plasmid pUC57-HRE-JAB1 driven by hypoxia response elements promoter was constructed first and then the plasmid along with chemotherapeutic drug such as cis-diamminedichloroplatinum（C-DDP） was introduced into lung cancer cell line A549 to treat A549 cells.RFPCR and western blot were used to assay the mRNA and protein level of JAB1.Cell cycle and apoptosis of A549 cells were also assayed after the transfection.Results The results showed that JAB1 gene in the A549 was overexpressed after the transfection of pUC57-HRE-JAB1 compared with that in control group and blank group（P〈0.05）.The cell proliferation was arrested at G1 phase and the cell apoptosis was significantly enhanced after the transfection（P〈0.01）.Importantly,pUC57-HRE-JAB1 introduction significantly increased the chemotherapeutic susceptibility of A549 to C-DDP.Conclusion Hypoxia-inducible factor 1 promoter-induced JAB1 overexpression significantly increased the chemotherapeutic sensitivity of lung cancer cells.It might provide an efficient strategy to overcome the chemotherapeutic resistance of lung cancer.

关 键 词：肺癌 缺氧诱导因子 JAB1 耐药 顺铂 

分 类 号：R734.2[医药卫生—肿瘤] R453[医药卫生—临床医学]