Recombinant IFN-α2a-NGR exhibits higher inhibitory function on tumor neovessels formation compared with IFN-α2a in vivo and in vitro

摘要

We previously reported that NGR-fused IFN-α2a (IFN-α2a-NGR) exhibited similar biological activities with native IFN-α2a and was well-tolerated in mice, rats and monkeys. In the current study, we evaluated the mechanisms of this fusion protein on angiogenesis and tumor formation. Our data indicated that IFN-α2a-NGR has the ability to target tumor blood vessels while preserving the original function of native IFN-α2a. IFN-α2a-NGR was found to be concentrated in the tumor tissues, particularly around the vessel areas. In contrast to IFN-α2a, IFN-α2a-NGR significantly decreased microvessel density and increased the apoptosis of vascular endothelial cells. IFN-α2a-NGR also decreased the expression of VEGF and bFGF in tumor cells. Significant inhibition of invasion, migration, tube formation and induction of apoptosis of endothelial cells were observed in IFN-α2a-NGR-treated group. In conclusion, results from in vitro and in vivo experiments indicate that IFN-α2a-NGR is a promising anti-angiogenic agent with greater therapeutic efficacy than IFN-α2a.Electronic supplementary materialThe online version of this article (doi:10.1007/s10616-014-9743-y) contains supplementary material, which is available to authorized users.