Indomethacin inhibits endothelial cell proliferation by suppressing cell cycle proteins and PRB phosphorylation: a key to its antiangiogenic action?
Mol Cell Biol Res Commun
; 4(2): 111-6, 2000 Aug.
Article
de En
| MEDLINE
| ID: mdl-11170841
ABSTRACT
Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit angiogenesis in vivo and in vitro, but the mechanism of this action is unclear. Angiogenesis-formation of new capillary vessels-requires endothelial proliferation, migration, and tube formation. It is stimulated by basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF). The cell cycle is regulated positively by cyclins and negatively by cyclin-dependent kinase inhibitors (CKI) and the retinoblastoma protein (pRb). Since the effects of NSAIDs on cell cycle-regulatory proteins in endothelial cells remain unknown, we examined the effect of indomethacin on bFGF-stimulated endothelial cell proliferation and on cell cycle regulatory proteins in rat primary aortic endothelial cells (RAEC). Indomethacin significantly inhibited basal and bFGF-stimulated endothelial cell proliferation. This inhibition correlated significantly with reduced cyclin D1 and increased p21 protein expression. Furthermore, indomethacin reduced pRb phosphorylation. These findings suggest that indomethacin arrests endothelial cell proliferation essential for angiogenesis by modulating cell cycle protein levels.
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Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Endothélium vasculaire
/
Anti-inflammatoires non stéroïdiens
/
Indométacine
/
Protéine du rétinoblastome
/
Protéines du cycle cellulaire
/
Protéines du muscle
Limites:
Animals
Langue:
En
Journal:
Mol Cell Biol Res Commun
Sujet du journal:
BIOLOGIA MOLECULAR
Année:
2000
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique