新城疫病毒对小细胞肺癌裸鼠移植瘤生长的抑制作用

Inhibitory effect of Newcastle disease virus on the growth of human small cell lung cancer xenografts

目的:探讨新城疫病毒(Newcastle disease virus,NDV)7793株在体内对肿瘤生长的抑制作用及机制。方法:体外培养人小细胞肺癌NCI-H446细胞,通过皮下接种NCI-H446细胞建立人小细胞肺癌裸鼠移植瘤模型。NDV组裸鼠瘤内注射新城疫病毒,阳性对照组注射顺铂(cisplatin,DDP),阴性对照组注射PBS。观察移植瘤生长情况和裸鼠体质量变化,绘制肿瘤生长曲线。6周后处死裸鼠剥取肿瘤组织,HE染色观察细胞学变化,免疫组织化学法检测移植瘤细胞Bax和Bcl-2蛋白表达情况。结果:NDV注射对肿瘤生长有显著抑制作用,抑瘤率达34.1%;NDV对荷瘤鼠无不良反应;光学显微镜下观察发现,NDV治疗组肿瘤组织有许多散在分布的凋亡/坏死区域。NDV能明显上调Bax蛋白的表达量(P<0.01),对Bcl-2蛋白表达则无影响。结论:新城疫病毒7793株在体内能够有效抑制移植瘤生长,其抗肿瘤机制可能与上调Bax蛋白的表达有关。

Objective：To investigate the inhibitory effects of Newcastle disease virus （NDV） 7793 on the growth of human small cell lung cancer xenografts in vivo and its possible anti-tumor mechanism. Methods ： Human small cell lung cancer NCI-H446 cells were cultured in vitro and inoculated into nude mice by subcutaneous injection to establish a xenografted model of human small cell lung can- cer in nude mice. Mice with xenografted tumor were randomized into three groups： NDV group （ NDV treatment） , positive control group （ cisplatin treatment） and negative control group （ PBS treatment）. NDV was injected into nude mice intratumorally. Tumor volume and body weight of mice were recorded at regular time intervals, then the tumor growth curve was drawn. The mice were killed and tumor tissues were removed after 6 weeks. HE staining was performed to observe the pathological changes of tumor cells. The expressions of apoptosis-related proteins Bax and Bcl-2 were analyzed by SP immunohistochemical method. Results： NDV injection significantly inhibited tumor growth and the tumor growth inhibition rate reached 34.1%. No obvious toxicity was observed in nude mice after NDV injection. Pathological examination found that there were more apoptosis/necrosis regions in tumor tissues of NDV group compared with negative control group. NDV markedly up-regulated expression of Bax protein （P 〈 0.01 ） but had no effects on Bcl-2 protein expression. Conclusion： NDV 7793 strain effectively inhibited the growth of xenografted tumor in vivo. The anti-tumor mechanism may be due to up-regulation of the expression of Bax protein.