Effect Of Endothelin-1 On Cyclooxygenase-2 Expression In Human Hormone Refractory Prostate Cancer Cells

Objective: To explore the effects and possible mechanism of recombinant human endothelin-1(ET-1) on cyclooxygenase-2 (COX-2) expression in human androgen independent refractory prostate cancer (AIPC) cells (PC-3 cells).Methods: PC-3 cells were treated with 100nmol/L ET-1 for indicated hours(3, 6, 9, 12, 24h)and indicated concentration (0.1, 1, 10, 100 nmol/L) for 24 h. Besides, 100 nmol/L ET-1 was used to treat PC-3 cells alone or in combination with endothelin A receptor(ETAR)antagonist BQ-123(1μmol/L), endothelin B receptor(ETBR)antagonist BQ788 (1μmol/L), MAPK/extracellular signalregulated kinase kinase (MEK)-selective inhibitor, PD98059 (10μmol/L), p38 mitogen activated protein kinase (MAPK) antagonist SB203580 (5μmol/L) and epidermal growth factor receptor (EGFR) antagonist AG1478(0.1μmol/L)for 24h. COX-2 mRNA and protein expression in PC-3 cells was detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis.Results: ET-1 induces a time and dose-dependent increase in mRNA or protein expression of COX-2 in PC-3 cells. BQ123, PD98059, SB203580 and AG1478 could prevent the expression of COX-2 in PC-3 cells (P<0.05) while BQ-788 couldn't. Conclusion: ET-1 could induce the up-regulation of COX-2 in PC-3 cells. ETAR might be involved in the course. Several signaling pathways, including p42/44 MAPK, p38 MAPK and EGFR have been implicated in the regulation of COX-2 expression.