Ministry of Education Key Lab for Avian Preventive Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou, China.
Intervirology. 2012;55(4):276-86. doi: 10.1159/000328325. Epub 2011 Aug 24.
Naturally occurring strains of Newcastle disease virus (NDV) have demonstrated the potential to kill cancer cells in both preclinical and clinical studies. Previous studies showed that apoptin, the VP3 protein of chicken infectious anemia virus, is a p53-independent, Bcl-2-insensitive apoptotic protein with the ability to specifically induce apoptosis in transformed cells. In this study, we tested the hypothesis that apoptin enhances NDV-mediated tumor cell death.
Reverse genetics was used to engineer an oncolytic NDV strain, FMW, to express apoptin. The antitumor effects of the recombinant virus (rFMW/AP) were also evaluated in the tumor cell lines and tumor-bearing mice.
Compared to the parental strain FMW, rFMW/AP was more potent in killing A459 and SMMC7721 tumor cells. Recombinant NDV also exhibited higher efficacy in suppressing tumor growth in mice bearing A549-induced tumors. Furthermore, rFMW/AP did not display apparent toxic effects in either normal cells or control mice.
Our results suggest that the recombinant NDV expressing apoptin is a promising novel antitumor agent.
天然存在的新城疫病毒（NDV）株在临床前和临床研究中显示出杀死癌细胞的潜力。先前的研究表明，鸡传染性贫血病毒的 VP3 蛋白凋亡素是一种 p53 非依赖性、Bcl-2 不敏感的凋亡蛋白，能够特异性诱导转化细胞凋亡。在这项研究中，我们检验了凋亡素增强 NDV 介导的肿瘤细胞死亡的假设。
采用反向遗传学技术构建表达凋亡素的溶瘤性 NDV 株 FMW。还在肿瘤细胞系和荷瘤小鼠中评估了重组病毒（rFMW/AP）的抗肿瘤作用。
与亲本株 FMW 相比，rFMW/AP 对 A459 和 SMMC7721 肿瘤细胞的杀伤作用更强。重组 NDV 对抑制 A549 诱导的肿瘤小鼠肿瘤生长也表现出更高的疗效。此外，rFMW/AP 对正常细胞或对照小鼠均无明显毒性作用。
我们的结果表明，表达凋亡素的重组 NDV 是一种很有前途的新型抗肿瘤药物。
