新城疫鸡瘟病毒对裸小鼠人肺腺癌移植瘤的抑瘤作用及机制的研究

Anti-tumor effect of newcastle disease virus (NDV) on human lung adenocarcinoma xenografts

目的 观察新城疫鸡瘟病毒及其HN基因与F基因对裸小鼠人肺腺癌移植瘤的抗肿瘤作用 ,并探讨其机制。方法 建立人肺腺癌细胞系在裸小鼠体内移植瘤动物模型 ,两组实验组瘤体内分别一次局部注射NDV病毒及携带HN及F基因的质粒 (pSV HN及pSV F)作抗肿瘤研究 ,同时设PBS对照。观察 5周 ,绘制肿瘤生长曲线 ,处死后量瘤重 ,并作电镜和光镜检查 ,观察其病理学改变。结果 NDV及其基因的质粒 (pSV HN及pSV F)对裸小鼠人肺腺癌移植瘤的生长有明显的抑制作用 (抑瘤率分别为 71.62 %和 79.40 % )。NDV组及质粒组与对照组瘤重均值之间差异显著 (P <0 .0 1)。对照组 14 %的肿瘤发生肝及肺的转移。NDV组电镜下可见肿瘤细胞内NDV粒子出芽。结论 NDV对裸小鼠人肺腺癌移植瘤有明显的抑瘤作用。pSV HN及pSV F亦明显的抑制裸小鼠人肺腺癌移植瘤生长 ,其抑瘤作用机制与NDV选择性地在肿瘤细胞内增殖并导致肿瘤细胞凋亡及溶解肿瘤细胞有关 ,由此推测在此过程中HN及F基因可能起主要作用。

Objective To evaluate the anti tumor effects of NDV and two genes of virus(HN and F) on athymic mice with human adenocarcinoma xenografts, and to investigate the mechanisms of its oncolytic role. Methods The experimental model of lung adenocarcinoma xenograft was established. The two experimental groups of athymic mice were given intratumoral injections of NDV and plasmids only once, and compared with PBS controls in the same time. Measure the volume of tumors for 5 weeks and make a curve of the volume. These mice were killed after 5 weeks, and the weight of the tumors was measured. The histological and ultrastructral changes were observed by electromicroscope and microscope. Results After one injection of live NDV and plasmids, the tumor growth was significantly suppressed (The median inhibitory rate was 71.62% and 79.40% respectively). The median weight of tumor of mice treated with NDV was remarkably lower than that of mice treated with PBS, and that of the mice treated with plasmids (P<0.01). 14% of the control group had liver and lung metastasis of the tumor, but no metastasis was found in the experimental groups. A great quantity of NDV viron budding was found in the NDV group. Conclusion NDV could replicate in human lung adenocarcinoma xenografts, leading directly to a potent anti tumor effect after one injection of live NDV. During the oncolytic process, the gene HN and gene F may play an important role.