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目的 观察经动脉插管导入肿瘤坏死因子α(TNF α)和白细胞介素 2 (IL 2 )重组腺病毒对转移性大鼠肝癌模型的治疗作用。方法 用 2 93细胞扩增人TNF α(以下简称TNF)和IL 2重组腺病毒 ,并测定病毒滴度 ;取大鼠乳腺癌细胞株 (Walker 2 5 6 )转染至肝脏的荷瘤大鼠动物模型 ,经肝固有动脉分别注入不同剂量的重组腺病毒 ,首先确定人肿瘤坏死因子 (hTNF)基因的最适用量 ;然后分为hTNF组 ,人IL 2 (hIL 2 )组 ,hTNF +hIL 2组 ,病毒对照组 (LacZ组 )和培养液对照组进行治疗 ,观察大鼠生存期。结果 所制备的人TNF α和IL 2重组腺病毒滴度为 2× 10 9pfu/ml和 2 .1× 10 9pfu/ml。经肝固有动脉注射肿瘤坏死因子重组腺病毒 (Ad .hTNF)的适宜剂量为 1.0× 10 9pfu。治疗结果显示 ,单独注射TNF α或IL 2重组腺病毒能有效延长转移性肝癌大鼠的存活期 ;这两种重组腺病毒单独使用时 ,治疗效果之间存在显著性差异 ;联合应用这两种重组腺病毒比单一使用TNF α或IL 2重组腺病毒能更有效地延长荷瘤大鼠的存活期。结论 经肝动脉插管注射目的基因重组腺病毒 ,可能是基因治疗肿瘤的一种较为有效的途径 ,为细胞因子基因的临床应用打下了基础
Objective To observe the therapeutic effects of trans-arterial intubation with tumor necrosis factor alpha (TNF alpha) and interleukin 2 (IL 2) recombinant adenoviruses on metastatic rat hepatoma models. METHODS: Human TNF α (hereinafter referred to as TNF) and IL 2 recombinant adenoviruses were amplified with 293 cells, and the titer of the virus was determined; Tumor-bearing rats transfected with liver of rat breast cancer cell line (Walker 256) were used. In animal models, different doses of recombinant adenovirus were injected into the proper hepatic artery to first determine the most suitable amount of human tumor necrosis factor (hTNF) gene; then divided into hTNF group, human IL 2 (hIL 2) group, hTNF + hIL 2 Group, virus control group (LacZ group) and culture fluid control group were treated to observe the survival period of the rats. Results The titer of the recombinant adenoviruses of human TNFα and IL 2 prepared was 2×10 9 pfu/ml and 2.1×10 9 pfu/ml. The appropriate dose of injection of tumor necrosis factor recombinant adenovirus (Ad.hTNF) via the proper hepatic artery was 1.0 x 10 9 pfu. The results showed that the single injection of TNFα or IL 2 recombinant adenovirus can effectively prolong the survival of metastatic liver cancer rats; when these two recombinant adenoviruses are used alone, there is a significant difference between the therapeutic effects; Recombinant adenoviruses were more effective at prolonging the survival of tumor-bearing rats than using TNFα or IL 2 alone. Conclusion Injecting the target gene recombinant adenovirus into the hepatic artery may be a more effective way for gene therapy for tumors, laying the foundation for the clinical application of cytokine genes.