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目的:探讨Tie2介导的基因导入系统体内靶向转导p53基因治疗肺癌的效果。方法:应用双功能交联剂SMCC将Tie2配体寡肽GA3与PEI连接构建靶向Tie2的基因载体。体外试验将GA3-PEI/luciferase导入Tie2表达阳性的SPC-A1肺癌细胞与Tie2表达阴性的SMMC7721肝癌细胞中,24 h后检测luciferase活性。体内导入试验将GA3-PEI/β-gal复合物注射SPC-A1细胞裸鼠种植瘤周围皮下,同时设立PEI/β-gal组为对照;24 h后牺牲裸鼠,检测心、肝、脾、肺、肾和瘤体的β-gal表达。另外将另一批四周龄SPC-A1肺癌种植瘤裸鼠随机分为5组:(1)NS;(2)GA3;(3)p53;(4)PEI/p53;(5)GA3-PEI/p53;每组6只;皮下注射GA3-PEI/p53基因复合物,隔2天1次,并测量肿瘤长短径,计算瘤体积及抑瘤率。结果:GA3-PEI/luciferase组的luciferase活性在SPC-A1细胞中明显高于SMMC7721细胞(P<0.05)。在种植瘤中可见较多蓝染细胞,心、肝、脾、肾组织中几乎不见篮染,肺支气管黏膜除外。与对照组比较,GA3-PEI/p53治疗组对肿瘤生长有明显抑制作用(P<0.05),其抑瘤率为61.29%。结论:GA3基因导入系统靶向转导p53基因,显著抑制肿瘤生长。
Objective: To investigate the effect of Tie2-mediated gene transfer system targeting p53 gene in lung cancer in vivo. METHODS: Tie2 ligand oligopeptide GA3 was ligated with PEI using bifunctional crosslinker SMCC to construct a gene vector targeting Tie2. In vitro, GA3-PEI / luciferase was transfected into Tie2-expressing SPC-A1 lung cancer cells and Tie2-negative SMMC7721 hepatoma cells, and luciferase activity was detected after 24 h. In vivo introduction test GA3-PEI / β-gal complex was injected into SPC-A1 cells in nude mice subcutaneously around the xenografts and PEI / β-gal group was established as control. Β-gal expression in lung, kidney and tumor. Another 4-week-old SPC-A1 lung cancer xenografts were randomly divided into 5 groups: (1) NS; (2) GA3; (3) p53; (4) PEI / p53; p53; 6 in each group; subcutaneously injected GA3-PEI / p53 gene complex once every 2 days, and measured the length and the diameter of the tumor, calculate the tumor volume and tumor inhibition rate. Results: The luciferase activity of GA3-PEI / luciferase group was significantly higher than that of SMMC7721 cells in SPC-A1 cells (P <0.05). More visible in the implantation of tumor-stained blue dye cells, heart, liver, spleen, kidney tissue almost no basket dye, lung bronchial mucosa except. Compared with the control group, GA3-PEI / p53 treatment group significantly inhibited tumor growth (P <0.05), and the tumor inhibition rate was 61.29%. CONCLUSION: GA3 gene transduction system targets p53 gene transfection and significantly inhibits tumor growth.