AFP/ANGIO/TK靶向性融合基因治疗人原发性肝癌的效果观察

目的：研究pcDNA3／AFP／angio／tk靶向性融合基因系统对人原发性肝癌皮下移植瘤的治疗效果。方法：建立人原发性肝癌裸小鼠皮下移植瘤模型。将荷瘤裸小鼠随机分为5组（每组6只）：肿瘤对照组；空质粒组；GCV组；pcDNA3／angio／tk组及pcDNA3／AFP／angio／tk组。瘤内分别注射不同的质粒，同时于裸鼠腹腔内注射GCV，在第二次瘤内给药后第2天及第三次瘤内给药后第15天，分别处死裸鼠进行检测（每次3只）病理学检查；原位末端标记（TUNEL）法检查细胞原位凋亡；透射电镜观察细胞超微结构变化。结果：病理学检查结果显示，prDNA3／AFP／angio／tk融合基因瘤内注射可明显抑制肿瘤生长。TUNEL法检测显示．pcDNA3／AFP／angio／tk组凋亡指数明显高于肿瘤对照组。透射电镜观察细胞超微结构变化，发现pcDNA3／AFP／angio／tk组有明显的细胞凋亡发生。结论：pcDNA3／AFP／angio／tk靶向性融合基因系统可显著抑制肿瘤的生长，而且作用效果优于pcDNA3／angio／tk融合基因系统（P〈0.05）。

Observation of AFP/ANGIO/TK Targeted Fusion Gene Therapy of Human Primary Hepatocellular Carcinoma

Objective: To study the curative effect of the pcDNA3/AFP/angio/tk targeted fusion gene system on subcutaneously transplanted tumors of human primary hepatic carcinoma. Methods: The subcutaneous transplantation tumor model of nude mice with human primary liver cancer was established and the nude tumor-bearing mice were divided randomly into five groups (6 in each group), i.e., the control group, void-plasmid group, GCV group, pcDNA3/angio/tk group and pcDNA3/AFP/angio/tk group. The appropriate solutions were injected directly into the tumors and GCV intraperitoneal injection was administered simultaneously in the appropriate groups. Pathologic examination included detection of in situ apoptosis using TUNEL and observation by transmission electron microscope for changes in cell ultrastructure. Results: The results of pathologic examination indicated that intratumoral injection of pcDNA3/AFP/angio/tk could remarkably inhibit the growth of the tumor. Assessment by TUNEL and electron microscopy detected apoptosis in the pcDNA3/AFP/angio/tk group. Conclusion: The pcDNA3/AFP/angio/tk targeted fusion gene system markedly inhibits tumor growth, and the curative effect of the pcDNA3/AFP/angio/tk fusion gene system is superior to that of the pcDNA3/angio/tk fusion gene system (P<0.05).