Experimental studies on anti-tumor angiogenesis effect of phosphodiesterase (PDE2, PDE4) inhibitors / 肿瘤

ABSTRACT

Objective: The purpose of our study was to investigate the effect of phosphodiesterase (PDE2 and PDE4) inhibitors on the proliferation and migration of endothelial cells as well as angiogenesis in vivo. Methods: Human umbilical vein endothelial cells (HUVEC) were selected for investigation of angiogenesis in vitro and the C57BL/6N mouse for in vivo study. The effects of PDE2 inhibitor [Erythro-9-(2-hydroxy-3nonyl) adenine, ENHA] and PDE4 inhibitor (RP705) on the intracellular cAMP levels in HUVEC were detected by enzyme-linked immunosorbant assay (ELISA) and their effects on the proliferation and migration of HUVEC were also determined. The tumor-inhibiting effects of combined application of ENHA and RP705 were observed. Results: EHNA (25 μmol/L) and RP705 (15 μmol/L) specifically inhibited the proliferation and migration of HUVEC stimulated by vascular endothelial growth factor (VEGF) and increased the intracellular cAMP level in HUVEC. EHNA combined with RP705 inhibited tumor angiogenesis in vivo. The tumor inhibitory rate was 45.50% in C57BL/6N mouse after combined therapy with EHNA and RP705. Conclusion: These results strongly suggested that PDE2 and PDE4 might be new potential therapeutic targets in pathological angiogenesis.