纽卡斯尔病毒疫苗和白细胞介素-12对荷人卵巢癌裸鼠模型作用的实验研究

Study on the effect of Newcastle disease virus vaccine and interleukin-12 to the transplantable nude mice model of human ovarian cancer

目的:探讨纽卡斯尔病毒疫苗(ATV-NDV)和白细胞介素-12(IL-12)对3AO裸鼠皮下移植瘤的影响及其作用机制。方法:建立3AO裸鼠移植瘤模型,随机分为4组,每组10只。Ⅰ组注射ATV-NDV(0.2mL);Ⅱ组注射IL-12(100ng/kg);Ⅲ组注射IL-12(100ng/kg)加ATV-NDV(0.2mL);Ⅳ组为对照组,腹腔注射生理盐水0.2mL;观察各组裸鼠成瘤率、生存期和生存延长率及肿瘤生长曲线。流式细胞术(FCM)观察裸鼠移植瘤细胞凋亡率及细胞周期,双标记计数NK细胞比例;称取裸鼠脾脏质量;移植瘤瘤体及各组裸鼠肝、脾、肾行组织病理学变化检查。结果:治疗组在荷瘤裸鼠生长延长率,裸鼠移植瘤细胞凋亡率,NK细胞群计数,裸鼠脾脏重量方面明显高于对照组,Ⅲ组高于Ⅰ组和Ⅱ组。组织病理学检查各治疗组中均可见有肿瘤坏死,肿瘤内及周围有明显的淋巴细胞浸润。结论:ATV-NDV和IL-12对人卵巢癌裸鼠皮下移植瘤具有明显的抑制作用。IL-12可增强ATV-NDV对卵巢癌的抑制作用。

OBJECTIVE：To investigate the effect and the mechanism of autologous tumor cell vaccines-Newcastle disease virus-infected （ATV-NDV） and interleukin-12 （IL-12） on the tumor transplanted into nude mice subcutaneously with 3AO. METHODS： The subcutaneous nude mice model were established with human ovarian cancer cell strain 3AO and were randomly assigned to 4 groups,10 nude mice in every group. Ⅰ group were injected 0.2 mL ATV-NDV;Ⅱ group injected IL-12 100 ng/kg;Ⅲ group injected 100 ng/kg IL-12＋0.2 mL ATV-NDV simultaneously;Ⅳ group were controls which were injected intraperitoneally with normal saline 0.2 mL. The formation tumor rates,survival duration,survival prolongation rates and the tumor growth curve diagram of each group were observed. The apoptosis,cell cycle and NK cell cluster count of the transplanted tumor were detected by FCM. The nude mice spleens were weighed. The transplanted tumor,liver,spleen and kidney were checked by histopathological change examination. RESULTS： The treated groups were higher than the control group in the survival rate of nude mice,tumor cell apoptosis rate,NK cell number of the transplanted tumor and spleen weight of the nude mice. The Ⅲ treated group was higher than the Ⅰ and Ⅱ group. All the treated groups could be observed tumor necrosis,lymphocytes soakage in the tumor and around the tumor. CONCLUSIONS： The ATV-NDV and IL-12 all have inhibitory effect on the subcutaneous transplanted tumors of the nude mice. IL-12 can enhance the effect of ATV-NDV to the ovarian cancer.