| Literature DB >> 16647637 |
Philip Funovics1, Christine Brostjan, Anneliese Nigisch, Anna Fila, Anna Grochot, Katarzyna Mleczko, Halina Was, Guenter Weigel, Jozef Dulak, Alicja Jozkowicz.
Abstract
15-Deoxy-Delta(12,14)-prostaglandin-J(2) (15d-PGJ(2)) upregulates expression of vascular endothelial growth factor (VEGF), but may inhibit angiogenesis. We found that 15d-PGJ(2) (1-10muM) 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-PGJ(2) inhibited expression of VEGFR-1 and VEGFR-2 receptors both at mRNA and protein levels. This inhibition, however, was transient (observed after 6-12h, but not after 24h) and weak (20-30%), and could not fully explain inhibition of response to VEGF. Accordingly, proliferation was inhibited when 15d-PGJ(2) was added 24h after VEGF or in cells stimulated with basic fibroblast growth factor. Interestingly, 15d-PGJ(2) 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-PGJ(2) contributes to decrease in angiogenic response.Entities:
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Year: 2006 PMID： 16647637 PMCID： PMC1463995 DOI： 10.1016/j.prostaglandins.2006.02.002
Source DB: PubMed Journal: Prostaglandins Other Lipid Mediat ISSN： 1098-8823 Impact factor: 3.072