전립선암세포주에서 선택적 Cyclooxygenase-2 억제제와 Prostaglandin E2 수용체 효현제가 Endothelin계에 미치는 영향
The Effects of Selective Cyclooxygenase-2 Inhibitor and Prostaglandin E2 Receptor Agonists on the Endothelin Axis of Prostate Cancer Cells
김태형, 김영선, 명순철, 이성운, 김태흥, 원은하,
소속 상세정보
김태형 ( Kim Tae-Hyoung )
중앙대학교 의과대학 비뇨기과학교실
김영선 ( Kim Young-Sun )
중앙대학교 의과대학 비뇨기과학교실
명순철 ( Myung Soon-Chul )
중앙대학교 의과대학 비뇨기과학교실
이성운 ( Lee Sung-Woon )
중앙대학교 의과대학 비뇨기과학교실
김태흥 ( Kim Tae-Heung )
중앙대학교 의과대학 비뇨기과학교실
원은하 ( Won Eun-Ha )
중앙대학교 의과대학 비뇨기과학교실
KMID : 0358320060470020195
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 (ETAR), 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, ETAR, 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, ETAR and ECE-1 were detected, and then the mRNA expressions of PPET-1, ETAR 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 10-6M.
Results: PPET-1, ETAR 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, ETAR and ECE-1 mRNA expressions, compared with the NS-398 treated group (control), in the PC-3 cells.
Conclusions: ET-1/ETAR 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 ETAR would be novel approach to prostate cancer therapy. (Korean J Urol 2006;47:195-200)
키워드
Prostate cancer;Cells;Cyclooxygenase-2;PGE2 receptors;Endothelins
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