Role of Peroxisome Proliferator-Activated Receptor Alpha in the Control of Cyclooxygenase 2 and Vascular Endothelial Growth Factor: Involvement in Tumor Growth

A growing body of evidence indicates that PPAR (peroxisome proliferator-activated receptor) alpha agonists might have therapeutic usefulness in antitumoral therapy by decreasing abnormal cell growth, and reducing tumoral angiogenesis. Most of the anti-inflammatory and antineoplastic properties of PPAR ligands are due to their inhibitory effects on transcription of a variety of genes involved in inflammation, cell growth and angiogenesis. Cyclooxygenase (COX)-2 and vascular endothelial growth factor (VEGF) are crucial agents in inflammatory and angiogenic processes. They also have been significantly associated to cell proliferation, tumor growth, and metastasis, promoting tumor-associated angiogenesis. Aberrant expression of VEGF and COX-2 has been observed in a variety of tumors, pointing to these proteins as important therapeutic targets in the treatment of pathological angiogenesis and tumor growth. This review summarizes the current understanding of the role of PPARalpha and its ligands in the regulation of COX-2 and VEGF gene expression in the context of tumor progression.