目的：研究血管生成抑制剂TNP-470联合5-FU对结肠癌肝转移的抑制作用。方法： 将结肠癌LOVO细胞注入裸鼠脾脏，建立结肠癌肝转移模型。将裸鼠随机分为联合治疗组、TNP-470组、5-FU组和对照组4组。治疗4周后，处死裸鼠，计数肝转移率和肝转移结节数。采用免疫组化SABC法和图像分析系统对肝转移肿瘤组织的微血管密度（MVD）和血管内皮生长因子（VEGF）的表达进行定量分析。结果：TNP-470+5-FU组和TNP-470组与对照组比较，肝转移率显著下降（P<0.01, P<0.01）；TNP-470+5-FU组和5-FU 组与对照组相比，VEGF表达量明显下降（P<0.01, P<0.05）；TNP-470+5-FU组和TNP-470组与对照组相比，MVD也明显下降(P<0.01, P<0.01)。结论：TNP-470与5-FU联合应用具有协同效应，可显著抑制结肠癌的肝转移，为安全有效的抗肿瘤策略。

Objective: To study the effect of angiogenesis inhibitor TNP-470 combination with 5-FU on liver metastasis of human colon cancer.Methods:Human colon cancer cell line, LOVO cells, were injected intrasplenically into BALB/c nude mice to produce diffuse liver metastases. Mice were randomly divied into four groups: TNP-470 treated group, 5-FU treated group, TNP-470+5-FU treated group and control group. Animals were sacrificed after 4 weeks, and their livers were processed for histological examination. Liver metastatic rate and tumor foci in liver were counted. Tumor microvessel density (MVD) and vascular endothelial growth factor (VEGF) were determined by immunohistochemistry SABC method with image analyse system. Results: TNP-470 in combination with 5-FU and TNP-470 alone display a significant inhibitory effect on liver metastasis compared to the control (P<0.01, P<0.01). The expression of VEGF in the liver metastatic tumors was clearly inhibited by TNP-470 in combination with 5-FU and 5-FU alone compared to the control (P<0.01, P<0.05). The expression of MVD was also inhibited by TNP-470 in combination with 5-FU or TNP-470 alone compared to the control (P<0.01, P<0.01). Conclusion:The angiogenesis inhibitor TNP-470 in combination with 5-FU has additive effect and inhibitory activity against liver metastasis of human colon cancer, therefore, might be a safe and effective anti-tumor strategy.

广东省自然科学基金项目（013072）