Cyclooxygenase-2억제제의 N-butyl-N-(4-hydroxybutyl) nitrosamine 유도 백서 방광암의 유전자 발현에의 영향
The Effect of Cyclooxygenase-2 Inhibitor on the Gene Expression Profile of N-butyl-N-(4-hydroxybutyl) nitrosamine-induced Rat Urinary Bladder Cancer
권수미, 오혜영, 이은진, 김선일, 홍성준,
소속 상세정보
권수미 ( Kwon Soo-Mee )
연세대학교 의과대학 비뇨기과학교실
오혜영 ( Oh Hea-Young )
연세대학교 의과대학 비뇨기과학교실, 비뇨의과학연구소
이은진 ( Lee Eun-Jin )
연세대학교 의과대학 비뇨기과학교실, 비뇨의과학연구소
김선일 ( Kim Sul-Il )
한양대학교 의과대학 비뇨기과학교실
홍성준 ( Hong Sung-Joon )
연세대학교 의과대학 비뇨기과학교실
KMID : 0358320060470030310
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.
Conclusion: 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. (Korean J Urol 2006;47:310-315)
키워드
Butylhydroxybutylnitrosamine;Bladder cancer;Angiogenic factor;cDNA microarray;Rats
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