Double suicide genes driven by kinase domain insert containing receptor promoter selectively kill human lung cancer cells.
Double suicide genes driven by kinase domain insert containing receptor promoter selectively kill human lung cancer cells.
复制标题
由含有受体启动子的激酶结构域插入物驱动的双自杀基因选择性地杀死人肺癌细胞。
DOI：
10.1186/1479-0556-9-6
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发表时间：
2011-03-22
期刊：
影响因子：
--
通讯作者：
Che, Guowei
中科院分区：
文献类型：
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作者：
Ma, Junrong;Li, Mi;Che, Guowei
背景：探讨KDR启动子驱动的双自杀基因的选择性杀伤效果。 材料与方法：构建KDR启动子双自杀基因系统pcDNA3-KDRp-CDglyTK，并转染肺癌细胞系L9981、NL9980和人肝癌细胞系HepG2。通过体外细胞增殖和凋亡以及体内异种移植研究来测定双自杀基因系统的效率和特异性。结果：转基因CD和TK基因仅在L9981和NL9980中表达，而在HepG2细胞中不表达。用 5-Fc 和 GCV 预处理转染细胞可显着减少 L9981 和 NL9980 细胞的增殖，增强细胞凋亡，但在 HepG2 细胞中则不然。具有双自杀基因系统的L9981和NL9980细胞在体内形成的肿瘤要小得多。结论：由KDR启动子驱动的CDglyTK基因的肿瘤靶向表达代表了具有内在KDR的肿瘤的有效基因治疗的新策略。
BACKGROUND: To investigate the selective killing efficacy of the double suicide genes driven by KDR promoter.MATERIALS AND METHODS: A double suicide gene system with the KDR promoter, pcDNA3-KDRp-CDglyTK, was constructed and transfected into lung cancer cell lines L9981 and NL9980, and human hepatocellular carcinoma cell line HepG2. The efficiency and specificity of the double suicide gene system were assayed by in vitro cellular proliferation and apoptosis, as well as in vivo xenograft studies.RESULTS: The transgenic CD and TK genes were only expressed in L9981 and NL9980 but not in HepG2 cells. Pre-treating transfected cells with 5-Fc and GCV significantly reduced proliferation, enhanced apoptosis in L9981 and NL9980 but not in HepG2 cells. The tumor formed by L9981 and NL9980 cells with the double suicide gene system was much smaller in vivo.CONCLUSION: Tumor targeted expression of CDglyTK gene driven by KDR promotor represents a novel strategy for effective gene therapy of tumor with intrinsic KDR.