目的：以脾脏保留法建立结肠癌小鼠肝转移模型，评价新城疫病毒（Newcastle disease virus，NDV）7793株对小鼠结肠癌肝转移的抑制效果，并初步探讨NDV抑瘤的免疫激活机制。方法：经脾注入1×107/ml小鼠结肠癌细胞CT26的单细胞悬液0.1 ml，建立结肠癌CT26小鼠肝脏转移瘤模型；建模小鼠随机分3组（每组20只）: PBS阴性对照组、NDV7793给药组和5-FU给药组，于建模当天起连续5 d经腹腔分别注射PBS(0.1 ml/d)、NDV7793(512 HU/kg)和5-FU(20 mg/kg)。观察各组小鼠的生存状态，分析肝脏成瘤情况，计算抑瘤率和胸腺指数。ELISA法检测模型小鼠肝脏的IFN-γ水平。结果：成功构建小鼠结肠癌肝转移模型。NDV7793给药组小鼠未观察到明显的不良反应，生活状态好于PBS组和5-FU组。NDV7793组和5-FU组小鼠的肝转移瘤数量较PBS组均显著减少\[ (20.40±5.20) 、(205.50±19.21) vs (265.30±35.73)个，均 P <0.01\]，NDV7793组的抑瘤率明显高于5-FU组（75.4% vs 48.0%， P <0.05），NDV7793组小鼠的肝脏癌灶范围小，癌细胞以坏死或凋亡为主。NDV7793组和5-FU组小鼠的中位生存期明显长于PBS阴性对照组（30、22 vs 17 d， P <0.01）。NDV7793组小鼠肝脏IFN-γ的表达和胸腺指数均显著高于5-FU组和PBS组（均 P <0.05）。结论：NDV7793株对结肠癌小鼠的肝转移具有较强的抑制效果，并可能通过上调肝脏的IFN-γ以及提升胸腺指数来抑制结肠癌的肝转移。

Objective: To evaluate the liver metastasis-inhibiting and immune-stimulating effects of Newcastle disease virus (NDV) strain 7793 in a mouse model of colon cancer. Methods: CT26 colon cancer cells (1×106 cells in 0.1 ml PBS) were injected into the subcapsules of the spleen of BALB/c mice aged 4-6 weeks through intra-peritoneal injection. Surviving mice bearing CT26 colon cancer cells were randomized to receive PBS (0.1 ml/d), NDV7793 (512 HU/kg) and fluorouracil (5-FU, 20 mg/kg), respectively, for 5 days. Body weight and general health status were recorded before colon cancer cell transplantation, before the designated treatments and on post-treatment days 1, 5, 10 and 15, respectively. On post-treatment day 16, animals were sacrificed. Liver metastasis was assessed gross pathology. Thymus and liver were collected. Histologic assessment was performed on paraffin sections of the liver after H-E staining. Thymus index and metastasis inhibition rate were calculated. IFN-γ levels in the liver were measured by ELISA. Results: The metastatic foci in colon cancer cell-bearing mice were significantly less ( P <0.05) after treatment with NDV (20.40±5.20) and 5-FU (205.50±19.21) respectively than with PBS (265.30±35.73). Liver metastasis inhibition rate was significantly higher for NDV7793 than for 5-FU group (75.4% vs 48.0%, P ＜0.05). The mean survival time of colon cancer cell-bearing mice was 30 days after NDV7793 treatment, 22 days after 5-FU treatment but only 17 days after PBS treatment ( P< 0.05). Compared with PBS control group and 5-FU group, the increased Thymus index and liver concentrations of IFN-γ were significantly higher after treatment with NDV 7793 than with 5-FU and PBS respectively ( P ＜0.05). Conclusion: NDV 7793 appears effective to inhibit liver metastasis of colon cancer cells. This effect may be mediated by elevated IFN-γ in liver microenvironment.

教育部博士导师联合基金资助项目（No. 20124503110007）；广西自然科学基金资助项目（No. 2014GXNSFAA118244）；广西医学科学实验中心开放基金专项资助（No. KFJJ2011-21）；广西研究生教育创新计划资助项目 (No. YCBZ2012014)