The Effect of Cyclooxygenase-2 Inhibitor on the Gene Expression Profile of N-butyl-N-(4-hydroxybutyl) nitrosamine-induced Rat Urinary Bladder Cancer

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