Published online Feb 28, 2006.
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
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.
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).
Table 1
Primer sequence for RT-PCR
References
-
Korea Statistical Information System. National Statistical Office. Republic of Korea.Available from: URL: http://kosis.nso.go.kr.
-
-
Lara PN Jr, Meyers FJ. Treatment options in androgen-independent prostate cancer. Cancer Invest 1999;17:137–144.
-
-
Bandyopadhyay GK, Imagawa W, Wallace D, Nandi S. Linoleate metabolites enhance the in vitro proliferative response of mouse mammary epithelial cells to epidermal growth factor. J Biol Chem 1987;262:2750–2756.
-
-
Kim TH, Kim YS, Myoung SC, Lee JH, Won EH. Prostaglandin E receptor II and IV increase the expression of matrix metalloproteinase-7 in PC (prostate cancer)-3 cells. Korean J Urol 2004;45:478–484.
-
-
Usmani BA, Harden B, Maitland NJ, Turner AJ. Differential expression of neutral endopeptidase-24.11 (neprilysin) and endothelin converting enzyme in human prostate cancer cell lines. Clin Sci 2002;103 Suppl 48:S314–S317.
-
-
Yoshimatsu K, Golijanin D, Paty PB, Soslow RA, Jacobsson PJ, DeLellis RA, et al. Inducible microsomal prostaglandin E synthase is overexpressed in colorectal adenomas and cancer. Clin Cancer Res 2001;7:3971–3976.
-