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

Su,Qi; Jia,Rui-Peng; Lin,Jianzhong; Xu,Lu-Wei; Wang,Zi-Zheng; Li,Wen-Cheng; Wang,Shu-Kui

doi:10.3892/ol_00000087

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

Authors:
- Qi Su
- Rui-Peng Jia
- Jianzhong Lin
- Lu-Wei Xu
- Zi-Zheng Wang
- Wen-Cheng Li
- Shu-Kui Wang
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Affiliations: Department of Urology, Nanjing First Hospital Affiliated with Nanjing Medical University, Nanjing 210006, P.R. China
Published online on: May 1, 2010 https://doi.org/10.3892/ol_00000087
Pages: 495-499

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Abstract

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 (ETAR) antagonist BQ123 (1 µmol/l), endothelin B receptor (ETBR) 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. ETAR 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.

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