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Kim, Kim, Myung, Lee, Won, and Kim: The Effects of Selective Cyclooxygenase-2 Inhibitor and Prostaglandin E2 Receptor Agonists on the Endothelin Axis of Prostate Cancer Cells
Original Article
Korean Journal of Urology

Korean Journal of Urology 2006; 47(2): 195-200.

Published online: 28 February 2006

DOI: https://doi.org/10.4111/kju.2006.47.2.195

The Effects of Selective Cyclooxygenase-2 Inhibitor and Prostaglandin E2 Receptor Agonists on the Endothelin Axis of Prostate Cancer Cells

Tae Hyoung Kim, Young Sun Kim, Soon Chul Myung, Seung Woon Lee, Eun Ha Won, Tae Houng Kim

Department of Urology, College of Medicine, Chung-Ang University, Seoul, Korea.

Corresponding author (kthlmk@hanafos.com)

Received 30 August 2005       Accepted 8 October 2005

Copyright © 2006 The Korean Urological Association

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.

Keywords: Prostate cancer, Cells, Cyclooxygenase-2, PGE2 receptors, Endothelins

Figures and Tables

Fig. 1
PC-3 and DU-145 cells express preproET-1 (PPET-1), ET-1 receptor A (ETAR), and endothelin converting enzyme-1 (ECE-1) (M: marker, 1: PC-3, 2: DU-145).
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Fig. 2
Time course of the preproET-1 (PPET-1) mRNA expression in the PC-3 and DU-145 cells. The PPET-1 mRNA expression is decreased in the PC-3 cells at 4, 8 and 12 hours after NS-398 10µM treatment (C: control).
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Fig. 3
The preproET-1 (PPET-1) mRNA expression in the PC-3 and DU-145 cells after NS-398 and NS-398 treatment along with various concentration of EP2 and EP4 agonist. The EP2 and EP4 agonists induce an increase in the PPET-1 mRNA expression in the PC-3 cells compared with the NS-398 10µM treated group (control), but the PPET-1 mRNA expression is not changed in the DU-145 cells (1: NS-398 10µM treated group (control), 2, 3, 4: 1 with 10-10, 10-8, 10-6M of EP2 agonist, 5, 6, 7: 1 with 10-10, 10-8, 10-6M of EP4 agonist).
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Fig. 4
The ET-1 receptor A (ETAR) mRNA expression in the PC-3 and DU-145 cells after NS-398 and NS-398 treatment along with treatment with various concentration of EP2 and EP4 agonists. EP2 and EP4 agonists induce an increase in the ETAR mRNA expression in the PC-3 cells, compared with the NS-398 10µM treated group (control) of PC-3 cells, but the ETAR mRNA expression is not changed in the DU-145 cells (1: NS-398 10µM treated group (control), 2, 3, 4: 1 with 10-10, 10-8, 10-6M of EP2 agonist, 5, 6, 7: 1 with 10-10, 10-8, 10-6M of EP4 agonist).
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Fig. 5
The endothelin converting enzyme-1 (ECE-1) mRNA expression in the PC-3 and DU-145 cells after NS-398 and NS-398 treatment along with various concentration of EP2 and EP4 agonist treatment. EP2 and EP4 agonists induce an increase in the ECE-1 mRNA expression in the PC-3 cells, compared with NS-398 10µM treated group (control), but the ECE-1 mRNA expression is not changed in the DU-145 cells (1: NS-398 10µM treated group (control), 2, 3, 4: 1 with 10-10, 10-8, 10-6M of EP2 agonist, 5, 6, 7: 1 with 10-10, 10-8, 10-6M of EP4 agonist).
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Table 1
Primer sequence for RT-PCR
kju-47-195-i001

RT-PCR: reverse transcription polymerase chain reaction, PPET-1: preproendothelin-1, ETAR: endothelin receptor A, GAPDH: glyceraldehyde-3-phosphate dehydrogenase

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