Effects of 15d-PGJ2 on VEGF-induced angiogenic activities and expression of VEGF receptors in endothelial cells

15-Deoxy-Δ12,14-prostaglandin-J2 (15d-PGJ2) upregulates expression of vascular endothelial growth factor (VEGF), but may inhibit angiogenesis. We found that 15d-PGJ2 (1-10 μM) attenuated all VEGF-induced angiogenic activities in human umbilical vein endothelial cells (HUVEC). It blocked almost completely cell proliferation, potently reduced migration, assembly into tube-like network on matrigel, and growth of capillaries into collagen gel. 15d-PGJ2 inhibited expression of VEGFR-1 and VEGFR-2 receptors both at mRNA and protein levels. This inhibition, however, was transient (observed after 6-12 h, but not after 24 h) and weak (20-30%), and could not fully explain inhibition of response to VEGF. Accordingly, proliferation was inhibited when 15d-PGJ2 was added 24 h after VEGF or in cells stimulated with basic fibroblast growth factor. Interestingly, 15d-PGJ2 decreased activities of c-jun and c-myc in HUVEC and overexpression of c-myc attenuated its antiproliferative effects. This suggests that inhibition of this transcription factor by 15d-PGJ2 contributes to decrease in angiogenic response.