Korean J Urol.  2006 Feb;47(2):195-200. 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

• Kim TH
• Kim YS
• Myung SC
• Lee SW
• Won EH
• Kim TH

• KMID: 2294201
• DOI: http://doi.org/10.4111/kju.2006.47.2.195

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.

Keyword

Prostate cancer; Cells; Cyclooxygenase-2; PGE2 receptors; Endothelins

MeSH Terms

Axis, Cervical Vertebra*
Cell Line
Cyclooxygenase 2*
Dinoprostone*
Endothelin-1
Endothelins*
Polymerase Chain Reaction
Prostate*
Prostatic Neoplasms*
Receptors, Prostaglandin E
Reverse Transcription
RNA, Messenger
Cyclooxygenase 2
Dinoprostone
Endothelin-1
Endothelins
RNA, Messenger
Receptors, Prostaglandin E

Figure

• 

  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).

• 

  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).

• 

  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).

• 

  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).

• 

  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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