Peroxisome proliferator-activated receptors (PPARs) are well characterized nuclear hormone receptors (NHRs) in the superfamily of ligand-activated transcriptional factors. PPAR ligands have recently been demonstrated to affect proliferation, differentiation and apoptosis of different cancer cell types. The growth of any solid tumor depends on angiogenesis. Vascular endothelial growth factor (VEGF) plays a prominent role in vesical tumor angiogenesis regulation. VEGF is regulated by diverse developmental and hormonal signals, including eicosanoid ligands of PPAR. Previous studies have shown that the peroxisome proliferator-activated receptors (PPARgamma, alfa and beta) are expressed in four melanoma cell lines (A375, WM35, WM9, WM239).

The present study was undertaken to investigate whether PPAR ligands could inhibit proliferation of melanoma cell lines and influence expression and activity of VEGF and matrix metalloproteinase's MMP-9 and MMP-2.

Melanoma cells were treated with a PPAR ligand for 48 h. VEGF, MMP-9 and MMP-2 expression was analysed on mRNA level. In addition secreted VEGF protein was quantified by immunoassay and MMPs gelatinolytic activity was determined on zymograms. The proliferation of all the studied cell lines was inhibited by natural and synthetic ligands PPAR - linoleic acid, ciglitazone, fenofibrate, and carbacycline. Their application led also to decreased expressions of VEGF, MMP-9 and MMP-2 in all the cell lines. In addition VEGF protein secretions as well as gelatinolytic activities of MMP-9 and MMP-2 in the four melanoma cell lines were significantly inhibited by natural and syntetic PPARs ligands. We conclude that since PPAR ligands significantly inhibited proliferation of melanoma cells in vitro, and downregulated VEGF, MMP-9 and MMP-2 expression they potentially could as well inhibit invasion of treated cells through ECM. Agonists of this nuclear receptor might be exploited pharmacologically to inhibit pathological vascularization and migration of tumor cancer such as melanoma.

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