Angiogenesis inhibitor TNP-470 suppresses tumorigenesis in rat urinary bladder.

Abstract

The efficacy of the anti-angiogenic factor TNP-470, an analogue of fumagillin, in controlling the development of bladder tumors was investigated. The anti-angiogenic activity of TNP-470 was evaluated in vitro by its capacity to suppress the growth and migration of bovine capillary endothelial cells. To investigate its effect in vivo on the development of tumors, we instilled 0.5 microgram of TNP-470 dissolved in rat urine into heterotopically transplanted rat urinary bladders in which carcinogenesis had been initiated by N-methyl-N-nitrosourea. In vitro, TNP-470 selectively inhibited the growth and migration of endothelial cells. Instillation of TNP-470 shortly after treatment with carcinogen reduced the tumor incidence significantly (p < 0.05) as compared with that in control animals receiving urine only. TNP-470 suppresses the development of bladder tumors when the treatment is started at an early stage of neoplasia. It may be useful in preventing recurrences or new growth of bladder tumors.