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Inhibitory Effect of Liver Metastasis of Human Colon Cancer by TNP-470 in Combination with 5-FU
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Abstract:
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.
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