目的：研究NDV7793序贯5-FU 治疗方案对小鼠结肠癌肝转移的抑制效果，并初步探讨序贯联合用药对荷瘤小鼠免疫功能的影响。方法：采用脾内注射法建立小鼠结肠癌肝转移模型；将小鼠模型随机分为3组：PBS 阴性对照组（0．1 mL／d，10 d）、NDV7793组[512 HU／（kg·d），5 d]和NDV7793序贯5-FU组[512 HU／（kg·d），5 d ＋10 mg／（kg·d），5 d]。根据受试小鼠生存时间、体重变化、肝脏转移癌灶数、肝重等指标评价序贯用药效果；根据受试小鼠胸腺指数及肝脏IFN-γ的量初步观察序贯用药对荷瘤小鼠免疫功能的影响。结果：小鼠生存时间序贯给药组（32 d）长于NDV7793单独给药组（30 d）及PBS阴性对照组（17 d）（P ＜0．05）；转移癌结节序贯给药组（30．60±9．32）少于PBS阴性对照组（273．30±30．73）（P ＜0．05），但与NDV7793组（24．83±6．90）相比，两者均无统计学差异（P ＞0．05），序贯给药组小鼠肝重轻于 PBS 阴性对照组（P ＜0．05）；序贯给药组的胸腺指数低于 NDV7793组（P ＜0．05），但其 IFN-γ表达水平远高于 NDV7793组，差异具有统计学意义（P ＜0．05）。结论：NDV7793序贯5-FU 对小鼠结肠癌肝转移具有抑制效果；与NDV7793单独用药相比，序贯联合用药对荷瘤小鼠生存期的延长及免疫功能的激活，均有一定的提高。%Objective The anti-tumor effect by sequential treatment with Newcastle disease virus (NDV) strain 7793 and 5-FU in liver-metastases mice model was evaluated and immune-active response stimulated by sequential therapy was investigated. Methods Liver metastasis mice model was established by intra-peritoneal injection. The model mice were randomly divided into 3 groups, being given PBS (0.1 mL/d,10 d), NDV7793 [512 HU/(kg·d),5 d] and NDV7793[512 HU/(kg·d),5 d] + fluorouracil [5-FU,10 mg/(kg·d),5 d]. The effect on survival time,body weight,liver weight change and the formation of liver metastasis in tumor-bearing mice model were detected after different treatments in evaluating the regression of mice liver metastasis by sequential therapy. The detection of thymus index and IFN-γ concentrations in liver tissue of tumor-bearing mice model may indicate the stimulation of immune-active response by sequential therapy. Results The mean survival time of tumor-bearing mice treated with NDV7793 and 5-Fu sequentially was 32 d , which was significantly higher than those of tumor-bearing mice treated with NDV7793(30 d) or PBS injections (17 d), respectively (P< 0.05); The metastatic foci of tumor-bearing mice treated with NDV and 5-FU sequentially (30.60 ± 9.32) which was significantly less than those of tumor-bearing mice treated with PBS injection (273.30 ± 30.73), (P <0.05), seem quite similar to those treated with NDV (24.83 ± 6.90),(P > 0.05), and the liver weight was lighter than PBS (P < 0.05); Compared with NDV treatment, the decreased thymus index and increased amount of the effector IFN γ were observed in tumor-bearing mice treated with NDV 7793 and 5-FU sequentially (P <0.05). Conclusions The sequential therapy with Newcastle disease virus 7793 strain and 5-FU was observed to co-exert a significant suppressive effect in liver metastases of colon cancer cells in tumor-bearing mice model. Compared with NDV treatment , the survival time of mice model and the induction of antitumor effector molecules were significantly improved after sequential therapy.
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