Therapeutic effect of TNP-470 on spontaneous liver metastasis of colon tumors in the rabbit

Even though angiogenesis inhibitor is thought to be one of the promising ag ents in tumor dormancy therapy, its optimal administration is still unknown . Therefore, the efficient protocol using TNP-470 was examined regarding it s treatment affect against spontaneous liver metastases of colon tumors in the rabbit. A spontaneous liver metastases model was established in the rab bit by the inoculation of VX-2 tumors into the subserosal space of the colo n. The therapeutic effect of TNP-470 was then investigated by monitoring bo th the number of metastatic nodules in the Liver and the microvessel densit y (MVD) in the tumor by immunohistochemical staining using anti-CD31 monocl onal antibody. TNP-470 did not show any effect on the primary tumor. It was able to reduce the metastatic spread to liver when it was administered at the microscopic metastatic stage. Treatment at this stage, however? was not able to sufficiently control the disease. These results indicated that TNP -470 could efficiently cause the tumor to enter into a dormant state by inh ibiting angiogenesis when it was used at the initial stage of the metastati c process in the liver. Regarding its clinical application, TNP-470 might b e useful for preventing the metachronous liver metastases of colorectal can cer when it is administered as adjuvant therapy after curative surgery.