The antiangiogenic effects of
TNP-470 on the neovascularization of
tumors were studied by examining ultrastructural alterations in the vasculature and interstitial fluid pressure (IFP) of
tumors. Wistar rats were first inoculated subcutaneously (s.c.) with the Walker 256
carcinosarcoma cell line, then either vehicle medium or
TNP-470, 30 mg/kg, was injected s.c. on day 1. A
tumor growth assay, the necrotic area, and the IFP in the
tumor were all measured on day 12. The antiangiogenic effects of
TNP-470 were studied by scanning electron microscopic images of
tumor vascular casts.
TNP-470 was observed to inhibit
tumor growth and increase the necrotic area significantly. In the TNP-470-treated group, the IFP in the superficial layer, defined
as 2-3 mm from the
tumor capsule, and in the deep layer, defined
as 8-10 mm from the
tumor capsule, were significantly higher than the corresponding values in the control. Moreover, vascular casts showed a significant reduction in the budding of sprouts in the superficial layer, and a decrease in the maximum diameter of the
tumor vessels in the deep layer. It is possible that the higher IFP in the TNP-470-treated
tumors might have prevented
tumor vessel dilation. The findings of this study demonstrated that
TNP-470 inhibited the budding of
tumor vessel sprouts, and increased the IFP. These processes seem to act synergistically to suppress
tumor angiogenesis.