Inhibitory effect of etodolac, a selective cyclooxygenase-2 inhibitor, on stomach carcinogenesis in Helicobacter pylori-infected Mongolian gerbils.
The effect of the selective COX-2 inhibitor, etodolac, on Helicobacter pylori (Hp)-associated stomach carcinogenesis was investigated in Mongolian gerbils (MGs). Hp-infected MGs were fed for 23 weeks with drinking water containing 10 ppm N-methyl-N-nitrosourea. They were then switched to distilled water and placed on a diet containing 5-30 mg/kg/day etodolac for 30 weeks. We found that etodolac dose-dependently inhibited the development of gastric cancer, and no cancer was detected at a dose of 30 mg/kg/day. Etodolac did not affect the extent of inflammatory cell infiltration or oxidative DNA damage, but it significantly inhibited mucosal cell proliferation and dose-dependently repressed the development of intestinal metaplasia in the stomachs of Hp-infected MGs. These results suggest that COX-2 is a key molecule in inflammation-mediated stomach carcinogenesis and that chemoprevention of stomach cancer should be possible by controlling COX-2 expression or activity.
Magari
Hirohito
H
Second Department of Internal Medicine, Wakayama Medical University, Wakayama 641-0012, Japan.
Shimizu
Yasuhito
Y
Inada
Ken-ichi
K
Enomoto
Shotaro
S
Tomeki
Tatsuji
T
Yanaoka
Kimihiko
K
Tamai
Hideyuki
H
Arii
Kenji
K
Nakata
Hiroya
H
Oka
Masashi
M
Utsunomiya
Hirotoshi
H
Tsutsumi
Yutaka
Y
Tsukamoto
Tetsuya
T
Tatematsu
Masae
M
Ichinose
Masao
M
D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D017308:Etodolac / Q000008:administration & dosage*; D005849:Gerbillinae; D016481:Helicobacter Infections / Q000150:complications / Q000188:drug therapy*; D016480:Helicobacter pylori / Q000187:drug effects*; D008297:Male; D011230:Precancerous Conditions / Q000188:drug therapy* / Q000382:microbiology; D013274:Stomach Neoplasms / Q000209:etiology / Q000382:microbiology / Q000473:pathology* / Q000517:prevention & control*; D016896:Treatment Outcome
D016861:Cyclooxygenase Inhibitors; D017308:Etodolac