AFP/ANGIO/TK靶向性融合基因治疗人原发性肝癌的效果观察
Observation of AFP/ANGIO/TK Targeted Fusion Gene Ther apy of Human Pr imary Hepatocellular Car cinoma
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摘要: 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,pcDNA3/AFP/an-gio/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)。Abstract: To study the curative effect of pcDNA3/AFP/angio/tk targeted fusion gene system on subcutaneous transplantation tumor of human primary hepatic carcinoma. Methods: The subcutaneous transplantation tumor model of nude mouse with human primary liver cancer was constructed and the nude tumor- bearing mice were divided randomly into five groups (6 each group), i.e., the control group, void- plasmid group, GCV group, pcDNA3/angio/tk group and pcDNA3/AFP/angio/tk group. Different plasmas were directly injected into tumor and GCV intraperitoneal injection was given simultaneously based on variety of the groups. Pathologic examination included detection of in situ apoptosis using TUNEL method and observation by transmission electron microscope for change of cell ultrastructure. Results: The results of pathologic examination indicated that intratumoral injection of pcDNA3 AFP/angio/tk gene could remarkably inhibit the growth of tumor. Determination by TUNEL and electron microscope could detect the cell apoptosis in pcDNA3/AFP/angio/tk group. Conclusion: pcDNA3/ AFP/angio/tk targeted fusion gene system would remarkably inhibit the growth of tumor, and the curative effect of fusion gene system of the pcDNA3/AFP/angio/tk is superior to pcDNA3/angio/tk fusion gene (P<0.05).