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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 establish a liver metastasis model of colon cancer in mice by spleen preservation and to evaluate the inhibitory effect of Newcastle disease virus (NDV) 7793 against liver metastasis of colon cancer in mice and to explore the immune activation mechanism of NDV. Methods: The colon cancer CT26 mouse liver metastasis model was established by injecting 0.1 ml single cell suspension of 1 × 107 / ml colon cancer cell CT26 into the spleen. The model mice were randomly divided into 3 groups (20 in each group): PBS, NDV7793 and 5-FU groups were injected intraperitoneally with PBS (0.1 ml / d), NDV7793 (512 HU / kg) and 5-FU mg / kg). The survival status of mice in each group was observed, the liver tumorigenesis was analyzed, and the tumor inhibition rate and thymus index were calculated. ELISA method was used to detect the level of IFN-γ in liver of model mice. Results: The colon cancer liver metastasis model was successfully constructed. No significant adverse reactions were observed in NDV7793-treated mice, and their life status was better than those in PBS and 5-FU groups. The number of liver metastases in NDV7793 group and 5-FU group was significantly lower than that in PBS group [(20.40 ± 5.20), (205.50 ± 19.21) vs (265.30 ± 35.73), P <0.01] The tumor rate was significantly higher in the 5-FU group than in the 5-FU group (75.4% vs 48.0%, P <0.05). The NDV7793 group had a small range of hepatic foci, with necrosis or apoptosis predominating. The median survival of mice in NDV7793 and 5-FU groups was significantly longer than that in PBS-negative controls (30,22 vs 17 days, P <0.01). The liver IFN-γ expression and thymus index of NDV7793 group were significantly higher than that of 5-FU group and PBS group (all P <0.05). CONCLUSION: NDV7793 strain has a strong inhibitory effect on liver metastasis of colon cancer in mice and may inhibit hepatic metastasis of colon cancer by up-regulating hepatic IFN-γ and increasing thymus index.