RESUMEN

Two angiostatic fusion proteins (hAE and hEA) of human angiostatin (hAS) and endostatin (hES) proteins differed in tandem connection manner were constructed and evaluated for synergistic anti-angiogenic effects. The 65 kDa secreted fusion proteins from Pichia pastoris expression were verified by mass-spec analysis and western blotting assay. Luciferase reporter gene assay using VEGF promoter revealed that angiostatin-endostatin fusion protein (hAE) and its corresponding fusion gene delivery on Human Microvascular Endothelial Cells (HMEC-1) resulted in more potent synergistic anti-angiogenic effects than endostatin-angiostatin fusion protein (hEA). These facts suggest that the orientation of fusion genes between hAS and hES might be an important factor for developing therapeutic proteins.

Asunto(s)

Inhibidores de la Angiogénesis/farmacología , Angiostatinas/genética , Angiostatinas/farmacología , Endostatinas/genética , Endostatinas/farmacología , Expresión Génica , Inhibidores de la Angiogénesis/genética , Inhibidores de la Angiogénesis/metabolismo , Angiostatinas/metabolismo , Sinergismo Farmacológico , Endostatinas/metabolismo , Células Endoteliales/efectos de los fármacos , Humanos , Pichia/genética , Pichia/metabolismo , Regiones Promotoras Genéticas , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , Proteínas Recombinantes de Fusión/farmacología