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Endostatin (ES) is an endogenous angiogenesis inhibitor that has the ability to inhibit tumor growth and metastasis. However, its clinical application is limited by a number of disadvantages, such as poor stability, short half-life and the requirement of high doses to maintain its efficacy. The chemical modification on ES may offer a solution to these disadvantages. The aim of the present study was to evaluate the effects of ES, polysulfated heparin-endostatin (PSH-ES) and polyethylene glycol-endostatin (PEG-ES) on the endothelial cell proliferation and angiogenesis associated with corneal neovascularization (CNV) and to determine their mechanisms of action. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) was used to study the effects of ES and its derivatives on endothelial cell proliferation in vitro , and rabbits were used to evaluate the effects of ES and its derivatives on CNV in vivo . In the evaluation of CNV, the expression of vascular endothelial growth factor in the cornea was measured via immunohistochemistry and microvessels were counted. ES and its derivatives significantly inhibited endothelial cell proliferation in vitro (P&lt;0.05) and suppressed CNV in vivo . Among the compounds examined, ES most effectively inhibited endothelial cell proliferation in vitro (P&lt;0.05); however, PSH-ES and PEG-ES most effectively inhibited CNV in vivo (P&lt;0.05). These results indicate that PSH-ES and PEG-ES are candidate anti-angiogenesis drugs.

experimental and therapeutic medicine

Augmented anti-angiogenesis activity of polysulfated heparin-endostatin and polyethylene glycol-endostatin in alkali burn-induced corneal ulcers in rabbits