Abstract: Objective To investigate the effect of endothelin receptor B(ETR-B)antagonist, BQ788,and phosphatidylinositol-3 kinase(PI3K)inhibitor,LY294002,on the gene expression of osteopontin (OPN)in human melanoma cells A375.Methods A375 cells were cultured,and pretreated with 1μmol/L BQ788,20μmol/L and 50μmol/L LY294002,respectively,for 1 h before the addition of 100 nmol/L endothelin 3(ET-3)into the medium.Cells treated only with ET-3 served as the control.The mRNA and protein expres-sions of OPN were detected by RT-PCR and Western blot respectively.Results The mRNA and protein expressions of OPN were significantly decreased in A375 cells treated with BQ788,and in those treated with LY294002,as compared to those in the control cells(all P<0.05).The inhibitory effect of LY294002 at higher concentrations was more significant than that at lower concentrations(P<0.05).Conclusion ET3/ETR-B axis could upregulate the expression of OPN via activating the PI3K pathway in A375 cells.

Key words: Melanoma, Receptor, endothelin B, Endothelin-3, A375, Osteopontin