Inhibitory effects of etodolac, a selective COX-2 inhibitor, on the occurrence of tumors in colitis-induced tumorigenesis model in rats.
Ulcerative colitis (UC)-associated neoplasia is one of the complications seen in patients with long-standing UC. Based on many epidemiological studies, colitis is assumed to promote colon tumorigenesis. Tumorigenesis is known to be suppressed in rodents and humans by selective cyclooxygenase-2 inhibitors. However, whether these drugs would serve as protective agents against UC-associated neoplasia remains unclear. Therefore, using a colitis-induced tumorigenesis rat model, we investigated the effects of etodolac, a selective cyclooxygenase-2 inhibitor, on tumorigenesis. The following 4 groups were examined: group A, administered trinitrobenzene sulfonic acid and 1,2-dimethylhydrazine; group B, in addition to the treatment in group A, also received etodolac; group C, administered etodolac alone; and group D, did not receive any agent throughout the study and served as an untreated control. The rats were sacrificed 163 days after the start of experiment, and the number of aberrant crypt foci and tumors in the intestine were counted using a stereoscopic microscope following methylene blue staining. The mean number of aberrant crypt foci was 52.4 in group A, 18.9 in group B, 0 in group C and 0.5 in group D. A total of 9 tumors were observed in group A alone, with none in the remaining groups. The numbers of aberrant crypt foci and tumors in group B were significantly lower than in group A. Etodolac, a selective cyclooxygenase-2 inhibitor, suppresses the occurrence of aberrant crypt foci and tumors in colitis-induced tumorigenesis in rats.
Takeda
Jun
J
Department of Surgical and Molecular Pathology, Dokkyo University School of Medicine, Mibu, Shimotsuga, Tochigi 321-0293, Japan.
Kitajima
Kazuaki
K
Fujii
Shigehiko
S
Horiuchi
Hideki
H
Hori
Hiroshige
H
Chibana
Yoko
Y
Okuyama
Takashi
T
Tominaga
Keiichi
K
Ichikawa
Kazuhito
K
Ono
Yuko
Y
Teramoto
Tadahisa
T
Ohkura
Yasuo
Y
Imura
Joji
J
Shinoda
Motoo
M
Chiba
Tsutomu
T
Sakamoto
Choitsu
C
Kawamata
Hitoshi
H
Fujimori
Takahiro
T
D000818:Animals; D003092:Colitis / Q000150:complications*; D003110:Colonic Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D017308:Etodolac / Q000494:pharmacology* / Q000627:therapeutic use; D007422:Intestines / Q000187:drug effects / Q000473:pathology; D051381:Rats
D016861:Cyclooxygenase Inhibitors; D017308:Etodolac