Phosphorothioate oligodeoxynucleotides inhibit basic fibroblast growth factor-induced angiogenesis in vitro and in vivo

Angiogenesis is regulated by heparin-binding growth factors, such as basic fibroblast growth factor (bFGF), We investigated the effects of phosphorothioate-mediated oligodeoxynucleotides (PS-ODN) on bFGF-induced angiogenesis, Because PS-ODN are polyanions, they can also bind many heparin-binding proteins, On a basement matrix using a Matrigel matrix, we observed <50% tube formation by human umbilical endothelial cells with 10 mu M bFGF, vascular endothelial growth factor, or nuclear factor-kappa B (NF-kappa B) antisense and sense PS-ODN, while phosphodiester oligodeoxynucleotides (PO-ODNs) were not affected. The PS-ODN, but not the PO-ODN, inhibited the bFGF-induced rabbit corneal neovascularization. In albino rats, the NF-kappa B antisense PS-ODN showed a low rescue score for bFGF-dependent photoreceptor rescue because of their degradation by constant light exposure. However, antisense PS-ODN active against bFGF inhibited angiogenesis more strongly than did the antisense NF-kappa B PS-ODN, Because of the important role bFGF plays in angiogenesis, some PS-ODN may serve as potent antiangiogenic compounds that act through a combination of polyanionic phosphorothioate effects and a sequence-specific antisense mechanism.