Effect of endothelin-1 on cyclooxygenase-2 expression in human hormone refractory prostate cancer cells.

The present study aimed to explore the effects and possible mechanisms of recombinant human endothelin (ET)-1 on cyclooxygenase (COX)-2 expression in human hormone refractory prostate cancer PC3 cells. PC3 cells were treated with 100 nmol/l ET-1 for the indicated times (3, 6, 9, 12 and 24 h) and concentrations (0.1, 1, 10 and 100 nmol/l) for 24 h. Moreover, 100 nmol/l ET-1 was used to treat PC3 cells alone or in combination with endothelin A receptor (ET(A)R) antagonist BQ123 (1 μmol/l), endothelin B receptor (ET(B)R) antagonist BQ788 (1 μmol/l), MAPK/extracellular signal-regulated kinase kinase (MEK)-selective inhibitor, PD98059 (10 μmol/l), p38 mitogen-activated protein kinase (MAPK) antagonist SB203580 (5 μmol/l) or epidermal growth factor receptor (EGFR) antagonist AG1478 (0.1 μmol/l) for 24 h. COX-2 mRNA and protein expression was detected in the PC3 cells by reverse transcription-polymerase chain reaction and Western blot analysis. ET-1 induced a time- and dose-dependent increase in the mRNA and protein expression of COX-2 in the PC3 cells. BQ123, LY294002, SC203580 and AG1478 prevented the expression of COX-2 in the PC3 cells (P<0.05), while BQ788 did not. ET-1 induced the up-regulation of COX-2 in the PC3 cells. ET(A)R may be involved in the process. Several signaling pathways, including p42/44 MAPK, p38 MAPK and EGFR, are therefore implicated in the regulation of COX-2 expression.