Inhibitory effect of suramin in rat models of angiogenesis in vitro and invivo

The aim of the present study was to test the ability of the chemotherapeuti c agent suramin to inhibit angiogenesis in experimental models in vitro and in vivo. In the culture of rat aortic rings on fibronectin, suramin dose-d ependently inhibited vascular cell growth, achieving the maximal effect (me an - 88% versus controls, P < 0.05) at 400 mu g/ml. Image analysis showed t hat suramin could inhibit microvessel sprouting in fibrin from rat aortic r ings as evaluated by the ratio between the cellular area and the mean gray value of the sample (sprouting index); suramin at 50 mu g/ml significantly reduced the sprouting index from the control value of 0.35 +/- 0.04 to 0.14 +/- 0.02 mm(2)/gray level (P < 0.05). Likewise, the area occupied by cells was 19.2 +/- 1.8 mm(2) as compared with 41.8 +/- 4.2 mm(2) in controls (P < 0.05). In the rat model of neovascularization induced in the cornea by ch emical injury, suramin at 1.6 mg/eye per day reduced the length of blood ve ssels (0.7 +/- 0.1 mm as compared with 1.5 +/- 0.1 mm in controls, P < 0.05 ). In the same model the ratio between the area of blood vessels and the to tal area of the cornea (area fraction score) was decreased by suramin from 0.19 +/- 0.02 in controls to 0.03 +/- 0.003 (P < 0.05). Suramin given i.p. at 30 mg/kg per day markedly inhibited the neovascularization induced in th e rat mesentery by compound 48/80 or conditioned medium from cells secretin g the angiogenic protein fibroblast growth factor-3 (FGF-3). The area fract ion score in control rats treated with compound 48/80 was 0.31 +/- 0.03, an d this was reduced to 0.07 +/- 0.01 by suramin (P < 0.05), After i.p. admin istration of FGF-3 the area fraction score was reduced by suramin from 0.29 +/- 0.03 to 0.05 +/- 0.01 (P < 0.05). These results provide evidence that suramin exerts inhibitory effects on angiogenesis in both in vitro and in v ivo models.