The Effects of Selective Cyclooxygenase-2 Inhibitor and Prostaglandin E2 Receptor Agonists on the Endothelin Axis of Prostate Cancer Cells.
10.4111/kju.2006.47.2.195
- Author:
Tae Hyoung KIM
1
;
Young Sun KIM
;
Soon Chul MYUNG
;
Seung Woon LEE
;
Eun Ha WON
;
Tae Houng KIM
Author Information
1. Department of Urology, College of Medicine, Chung-Ang University, Seoul, Korea. kthlmk@hanafos.com
- Publication Type:Original Article
- Keywords:
Prostate cancer;
Cells;
Cyclooxygenase-2;
PGE2 receptors;
Endothelins
- MeSH:
Axis, Cervical Vertebra*;
Cell Line;
Cyclooxygenase 2*;
Dinoprostone*;
Endothelin-1;
Endothelins*;
Polymerase Chain Reaction;
Prostate*;
Prostatic Neoplasms*;
Receptors, Prostaglandin E;
Reverse Transcription;
RNA, Messenger
- From:Korean Journal of Urology
2006;47(2):195-200
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
PURPOSE: The enhanced expression of the cyclooxygenase-2 (COX-2), prostaglandin E2 receptor (EPs) and endothelin-1 (ET-1) axis is known to play a significant role in the development and progression of several malignancies. To date, little work has been done to investigate the relationships between the COX-2, EPs and ET-1 axis in prostate cancer (PC) cells. The aim of this study is to investigate the expression of preproET-1 (PPET-1), ET-1 receptor A (ET(A)R), and endothelin converting enzyme-1 (ECE-1) in the PC cell lines and to evaluate the effects of COX-2 and EPs on the expression of PPET-1, ET(A)R, and ECE-1. MATERIALS AND METHODS: Two PC cell lines, PC-3 and DU-145 cells were used for this study. By performing reverse transcription polymerase chain reaction (RT-PCR), the mRNA expressions of PPET-1, ET(A)R and ECE-1 were detected, and then the mRNA expressions of PPET-1, ET(A)R and ECE-1 were detected after being treating the cells with selective COX-2 inhibitor (NS-398), or EP2 (butaprost) and EP4 (misoprostol), which are both agonist of 10(-10), 10(-8) and 10(-6)M. RESULTS: PPET-1, ET(A)R and ECE-1 mRNA were expressed in both cell lines. After NS-398 treatment, only the PPET-1 mRNA expression was decreased at 4, 8 and 12 hours in the PC-3 cells. EP2 and EP4 agonist induced an increase for the PPET-1, ET(A)R and ECE-1 mRNA expressions, compared with the NS-398 treated group (control), in the PC-3 cells. CONCLUSIONS: ET-1/ET(A)R and ECE-1, whose expressions are increased by EP2 and EP4, may play key roles in the development and progression of PC via COX-2. A combination treatment with selective inhibitors for COX-2, EPs and ET(A)R would be novel approach to prostate cancer therapy.