J.Jpn. Surg. Soc.. 99(7): 441-445, 1998

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Feature topic

THERAPEUTIC EFFECT OF ANGIOGENESIS INHIBITORS ON LIVER METASTASES OF HUMAN COLORECTAL CARCINOMA

Angiogenesis is essential for the growth of solid tumors. Antiangiogenic therapy has therefore attracted considerable interest as a novel therapy for various tumors including colorectal carcinoma. We experimentally investigated the therapeutic effect of TNP-470, a nonspecific inhibitor of angiogenic factors, and vascular endothelial growth factor (VEGF)-neutralizing antibody (VEGFAb), was a VEGF-specific inhibitor, on liver metastases of colon carcinoma using a murine orthotopic transplantation model. TK-4 and TK-13 are moderately differentiated adenocarcinoma strains established in our department which express VEGF mRNA and protein. Administration of TNP-470 30 mg/kg significantly inhibited the liver metastases of both strains, as did administration of VEGFAb 100μg/mouse. The therapeutic effect on liver metastases was more dominant with antiangiogenic therapy than with chemotherapy (mitornycin C). Furthermore, the sustained effect of TNP-470 induced tumor dormancy and consequently improved the survival of the animals. These results suggest that antianigogenic treatment will be a potent therapy for liver metastases of human colorectal carcinoma in the future.

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