The Effect of Cyclooxygenase-2 Inhibitor on the Gene Expression Profile of N-butyl-N-(4-hydroxybutyl) nitrosamine-induced Rat Urinary Bladder Cancer.
10.4111/kju.2006.47.3.310
- Author:
Soo Mee KWON
1
;
Hea Young OH
;
Eun Jin LEE
;
Sun Il KIM
;
Sung Joon HONG
Author Information
1. Department of Urology, and the Urological Science Institute, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Korea. sjhong346@yumc.yonsei.ac.kr
- Publication Type:Original Article
- Keywords:
Butylhydroxybutylnitrosamine;
Bladder cancer;
Angiogenic factor;
cDNA microarray;
Rats
- MeSH:
Angiogenesis Inducing Agents;
Animals;
Apolipoproteins;
Butylhydroxybutylnitrosamine;
Carcinogenesis;
Cell Proliferation;
Cyclooxygenase 2*;
Gene Expression*;
Humans;
Incidence;
Male;
Neprilysin;
Oligonucleotide Array Sequence Analysis;
Prostaglandin-Endoperoxide Synthases;
Rats*;
Transcriptome*;
Urinary Bladder Neoplasms*;
Urinary Bladder*;
Celecoxib
- From:Korean Journal of Urology
2006;47(3):310-315
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
PURPOSE: Cyclooxygenase (COX)-2 plays an important role in promoting cancer cell proliferation and angiogenesis in human bladder cancer. In this study, we investigated the antitumor or antiangiogenic effects of selective COX-2 inhibitor on N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-induced rat bladder tumorigenesis. MATERIALS AND METHODS: Forty male Fischer 344 rats (control) were given only 0.05% BBN, while 40 rats (experimental) were administered 1,500mg/ kg celecoxib once daily and this treatment started from 1 week before their BBN treatment. Ten rats from the control groups and the experimental groups were then sacrificed at 4, 12, 16 and 24 weeks after BBN treatment. We observed all the bladders macroscopically as well as microscopically, and we measured the COX-2 expression in the bladder tissues. Utilizing a cDNA microarray, we analyzed the significant differences of gene expression between the 12 week-control group and the 12 week-experimental group. RESULTS: The incidence of tumor was lower in the experimental group than in the control group from week 12 to week 24. The COX-2 expressions were more significantly decreased via the BBN induction (p<0.05) in the experimental groups than in the control groups after 4 weeks. For the 12 week-experimental group, there were 15 genes altered by the administration of selective COX-2 inhibitor, and the selective COX-2 inhibitor especially regulated transgelin, membrane metallo endopeptidase and apolipoprotein E of these 15 genes to prevent the incidence of bladder tumor. CONCLUSIONS: Selective COX-2 inhibitor has an inhibitory effect on BBN-induced rat bladder tumorigenesis. In the pre-neoplastic phase, selective COX-2 inhibitor regulates transgelin, membrane metallo endopeptidase and apolipoprotein E to prevent the incidence of bladder tumor.
