Korean J Urol.  2003 Oct;44(10):1050-1057.

Effect of Selective Cyclooxygenase-2 Inhibitor on Apoptosis of the Human Prostate Cancer Cell Xenografted in Nude Mice

• Oh SY
• Shin JH
• Ahn JH
• Noh BS
• Ahn SH
• Kim TH
• Myoung SC
• Kim YS
• Bang HW
• Lee TJ

Abstract

PURPOSE: Cyclooxygenase (COX)-2, an inducible enzyme that catalyzes the formation of prostaglandins from arachidonic acid, is overexpressed in various cancers, including prostate cancer, and cell lines. COX-2 has been reported to play an important role in carcinogenesis. The aim of this study was to evaluate the effects of a selective COX-2 inhibitor (meloxicam) on the cell proliferation, apoptosis, Bcl-2, and Bcl-xL expression in prostate cancer.
MATERIALS AND METHODS
20 male nude mice were subcutaneously inoculated with 1 million PC-3 cells expressing COX-2. After 1 week, the mice were divided into two groups of 10 mice. Group 1 was left untreated, which served as a control. Group 2 was treated with meloxicam (40mg/kg) four times a week for 3 weeks. After the 4 weeks experimental period, the tumors were immunohistochemically assayed for apoptosis (TUNEL) and proliferation (Ki-67). The COX-2, Bcl-2 and Bcl-xL mRNA expression levels in the tumors were evaluated by RT-PCR.
RESULTS
The meloxicam had no effect on the tumor cell proliferation, but induced inhibition of PC-3 tumor cell growth and apoptosis. The Bcl-2 expression decreased in the meloxicam-treated group, but there was no significant difference between the two groups. The Bcl-xL expression was significantly down regulated in the meloxicam-treated group (p<0.01).
CONCLUSIONS
Our results suggest that a selective COX-2 inhibitor suppresses PC-3 cell tumor growth in vivo. Tumor growth suppression was achieved by the induction of tumor cell apoptosis, and was associated with a decreased Bcl-xL expression, which is one of the Bcl-2 related genes.

Keyword

Prostatic neoplasms; Cyclooxygenase-2; Meloxicam; Apoptosis

MeSH Terms

Animals
Apoptosis*
Arachidonic Acid
Carcinogenesis
Cell Line
Cell Proliferation
Cyclooxygenase 2*
Heterografts*
Humans*
Male
Mice
Mice, Nude*
Prostaglandin-Endoperoxide Synthases
Prostaglandins
Prostate*
Prostatic Neoplasms*
RNA, Messenger
Arachidonic Acid
Cyclooxygenase 2
Prostaglandin-Endoperoxide Synthases
Prostaglandins
RNA, Messenger