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

The aim of the present study was to test the ability of the chemotherapeutic agent suramin to inhibit angiogenesis in experimental models in vitro and in vivo. In the culture of rat aortic rings on fibronectin, suramin dose-dependently inhibited vascular cell growth, achieving the maximal effect (mean - 88% versus controls, P < 0.05) at 400 mu g/ml. Image analysis showed that suramin could inhibit microvessel sprouting in fibrin from rat aortic rings 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 chemical injury, suramin at 1.6 mg/eye per day reduced the length of blood vessels (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 total 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 the rat mesentery by compound 48/80 or conditioned medium from cells secreting the angiogenic protein fibroblast growth factor-3 (FGF-3). The area fraction score in control rats treated with compound 48/80 was 0.31 +/- 0.03, and this was reduced to 0.07 +/- 0.01 by suramin (P < 0.05), After i.p. administration 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 vivo models.