전립선암세포주 PC-3에서 Prostagladin E 수용체 Ⅱ, Ⅳ에 의한 Martrix Metalloproteinase-7의 발현 증가

Abstract

Purpose: The effects of PGE2 receptors(EP1, 2, 3, 4) on the proliferation of prostate cancer cells are still unclear. The degradation of the basement membrane by MMP-2, 7, 9 and TIMP-1, 2 is a critical point in tumor invasion and metastasis. We investigated the effects of PGE2 receptors concerning MMP and TIMP after the treatment of COX-2 inhibitors on prostate cancer cell-lines. Materials and Methods: Two prostate cancer cell-lines, PC-3 and DU-145 cells were used in this study. RT-PCR were performed to detect the mRNA expression of EP1, 2, 3, 4, MMP-2, 7, 9 and TIMP-1, 2, MMP-7 was measured by ELISA after being treated with the selective EP2 agonist and EP4 agonist 10-10, 10-8, 10-6μM respectively. Results: EP2, 3 and 4 mRNA were expressed in both cell-lines. After the NS-398 treatment, EP2 and EP4 mRNA expressions decreased in PC-3 cells. While only the MMP-7 mRNA expression decreased in PC-3 cells after NS-398 treatment, after NS-398 with selective EP2 agonist and EP4 agonist, MMP-7 mRNA expression increased. In PC-3 cells, selective EP2 agonist and EP4 agonist induced a significant dose-dependent increase in MMP-7 production in comparison to the NS-398 treatment group (control) in the conditioned ELISA medium. Conclusions: These results strongly suggest that COX-2, to some extent, contribute to prostate carcinogenesis at the EP2 and EP4 receptor, which could also be explained by increments of MMP-7 in PC-3 cells. Therefore, these findings show that selective EP inhibitor is useful in preventing specific disease progression in prostate cancer. (Korean J Urol 2004;45: 478-484)