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目的 观察瘤体内注射携带小鼠Flt3配体 (FL)基因的重组腺病毒载体对小鼠肝癌的治疗效果。方法 小鼠肝癌细胞株Hepa1 6皮下接种 ,建立小鼠肝癌模型 ,肿瘤局部分别单次注射 1× 10 9表达形成单位 (efu)的Flt3配体重组腺病毒、空载体对照和磷酸盐缓冲液 (PBS) ,观察肿瘤大小和小鼠生存期 ;3 8d后 ,再接种Hepa1 6细胞或EL4细胞对照于肿瘤消退小鼠原接种部位的对侧 ,观察肿瘤大小。结果 瘤体内注射Flt3配体重组腺病毒导致 90 %的小鼠肿瘤消退 ,并延长小鼠生存期 ,与对照组相比差异有显著性 (P <0 .0 0 2 ) ;再接种Hepa1 6细胞于肿瘤消退小鼠 ,未见肿瘤生长 ,而再接种的EL4细胞呈渐进性生长 ,与对照组相比差异无显著性 (P >0 .0 5 )。结论 腺病毒介导的小鼠Flt3配体的基因治疗导致肿瘤消退 ,并能激发特异性免疫保护反应。
Objective To observe the therapeutic effect of injecting recombinant adenovirus vector carrying mouse Flt3 ligand (FL) gene in mice on mouse liver cancer. Methods Mouse liver cancer cell line Hepa1 6 was inoculated subcutaneously to establish a mouse model of hepatocellular carcinoma. The tumor cells were injected with 1 × 10 9 recombinant eukaryotic expression vector (Flt3) recombinant adenovirus, empty vector control and phosphate buffered saline PBS). The tumor size and the survival period of mice were observed. On the 38th day after transplantation, Hepa16 cells or EL4 cells were inoculated to the opposite side of the mice inoculated with tumor cells to observe tumor size. Results In vivo injection of Flt3 ligand recombinant adenovirus resulted in tumor regression in 90% of mice and prolonged survival of mice, which was significantly different from that of control group (P <0. 02). Hepa1 6 cells There was no tumor growth in mice with tumor regression, while the re-inoculated EL4 cells showed progressive growth compared with the control group (P> 0.05). Conclusions Adenovirus-mediated gene therapy of murine Flt3 ligand leads to tumor regression and can stimulate specific immunoprotective responses.