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[摘要]
目的:寻求有效的肿瘤基因治疗方法,研究新城疫病毒HN基因与鸡贫血病毒VP3基因在无胸腺裸鼠体内的抗肿瘤作用。方法:建立BALB/c裸小鼠荷人结肠癌模型,瘤内注射脂质体包裹的真核重组子pVHN和pVVP3。观测pVHN和pVVP3治疗荷HCT裸鼠的效果,免疫组化法检测肿瘤细胞Bcl-2和PCNA的表达。结果:经HN基因和VP3基因联合治疗组的小鼠与荷瘤对照组小鼠相比,肿瘤体积明显缩小,抑瘤率可达70%。病理组织切片表明,治疗组裸鼠体内肿瘤细胞大量凋亡,局部地方可见细胞消失。免疫组化表明, Bcl-2和PCNA蛋白在荷HCT裸鼠对照组与各治疗组均有表达,其中Bcl-2表达在荷瘤对照组与pVHN治疗组差异有显著意义(P<0.05),PCNA表达在荷瘤对照组与pVHN+pVVP3治疗组差异极其显著(P<0.01)。结论: NDV HN基因与凋亡素VP3基因对裸鼠荷HCT肿瘤细胞的增殖有一定抑制作用,可诱导其凋亡,其凋亡可能与下调Bcl-2表达有关。
[Key word]
[Abstract]
Objective: The Explore the effective method of tumor gene therapy and studying the antitumor effect of NDV HN gene and apoptin VP3 gene.Methods: The carcinoma of colon model in BALB/c nude mice was constructed and the pVHN and pVVP3 DNA-liposome complexes were injected into the tumor. The therapeutic effect of NDV HN gene and apoptin VP3 gene to BALB/c nude mice bearing HCT tumor was observed. and the expressions of the Bcl-2 and PCNA of the tumors were detected with immunohistochemistry. Results: Compared with the control group ,the tumors in the group of combination therapy were decreased obviously,and the rate of suppressing tumor reached 70 percent. The results of pathological tissue section showed that apoptosis was induced greatly in the group of combination therapy,and the tumor cells in some range disappeared.The results of immunohistochemistry showed that the Bcl-2 and PCNA protein were expressed in control group and all of therapy groups , the Bcl-2 expression rates of control group and the therapy group with pVHN were marked difference (P<0.05) and the PCNA expression rates of control group and the therapy group with pVHN and pVVP3 were very marked difference (P<0.01) .Conclusion: NDV HN gene and apoptin VP3 gene are able to suppress the proliferation of the tumor cells in BALB/c nude mice bearing HCT tumor and induce apoptosis of the tumor cells. The apoptosis that induced by NDV HN gene and apoptin VP3 gene may correlated with down-regulation of Bcl-2 protein.
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[基金项目]
国家“973”资助项目(G1999011902)