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Chemopreventive effects of cyclooxygenase‐2 inhibitor and epidermal growth factor‐receptor kinase inhibitor on rat urinary bladder carcinogenesis
Author(s) -
HATTORI KAZUNORI,
IIDA KATSUYUKI,
JORAKU AKIRA,
TSUKAMOTO SADAMU,
AKAZA HIDEYUKI,
OYASU RYOICHI
Publication year - 2006
Publication title -
bju international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.773
H-Index - 148
eISSN - 1464-410X
pISSN - 1464-4096
DOI - 10.1111/j.1464-410x.2006.06053.x
Subject(s) - meloxicam , gefitinib , medicine , cox 2 inhibitor , hyperplasia , carcinogen , tyrosine kinase inhibitor , epidermal growth factor receptor , cyclooxygenase , urology , endocrinology , cancer , chemistry , enzyme , biochemistry , organic chemistry
OBJECTIVE To examine the chemopreventive effects of a selective cyclooxygenase (COX)‐2 inhibitor, meloxicam, and a selective epidermal growth factor (EGF)‐receptor tyrosine kinase inhibitor, gefitinib (as a single agent) on a carcinogen‐induced rodent bladder carcinogenesis model. MATERIALS AND METHODS The study comprised 103 male Fisher‐344 rats (8 weeks old); after initial carcinogen treatment for 8 weeks with 0.05% N ‐butyl‐ N ‐(4‐hydroxybutyl)nitrosamine (BBN) in drinking water, the rats were divided into five groups, i.e. group 1, control (vehicle only); group 2, gefitinib high‐dose (15 mg/kg by gavage once daily); group 3, gefitinib low‐dose (5 mg/kg); group 4, meloxicam high‐dose (1.8 mg/kg by gavage once daily); and group 5, meloxicam low‐dose (0.6 mg/kg). Twelve weeks later the rats were killed; after fixing the bladder in 10% formalin, the number and size of hyperplasia and carcinoma foci were recorded microscopically in sections stained with haematoxylin and eosin, submitted entirely as multiple strips. RESULTS The incidence of carcinoma, confirmed microscopically, was: control 14/20 (70%); high‐dose gefitinib, 7/20 (35%); low‐dose gefitinib, 7/20 (35%); high‐dose meloxicam 7/21 (33%); and low‐dose meloxicam, 12/20 (60%). The mean numbers of carcinomas per bladder in groups 1–5 were 1.2, 0.5, 0.4, 0.5 and 1.1, respectively. The incidence and the mean number of carcinomas per bladder were significantly lower in the treatment groups ( P < 0.05) than in the control group, except in the low‐dose meloxicam group. There were no significant adverse effects. CONCLUSION Both meloxicam and gefitinib have inhibitory effects on rat bladder carcinogenesis with no significant adverse effects. A combination of these drugs would be worth studying for their synergistic effects.