Short-term celecoxib intervention is a safe and effective chemopreventive for gastric carcinogenesis based on a Mongolian gerbil model.
OBJECTIVE
To evaluate the optimal intervention point of a selective cyclooxygenase-2 (COX-2) inhibitor, celecoxib, for inhibiting Helicobacter pylori (H. pylori)-associated gastric carcinogenesis in Mongolian gerbils (MGs).


METHODS
One hundred and twelve MGs were divided into six groups (A-F). One hundred gerbils were inoculated with H. pylori (groups A-E). Twelve gerbils were inoculated with vehicle broth only (group F). After 4 wk, they were given N'-methyl-N'-nitro-N-nitroso-guanidine (MNNG) (50 microg/mL) in the drinking water for 20 wk. In groups B-E, the animals were given the stock celecoxib (10 mg/kg per day) diet from the 21st, 31st, 21st and 41st week respectively. The periods of administering celecoxib were 30, 20, 20, and 15 wk respectively. On the 51st week, the animals were sacrificed for histological examination. Local PCNA expression was examined by the immunohistochemistry method. The expression of COX-2 protein was assessed by western blot. Analysis used the chi(2) test. The difference was regarded as significant when P value was less than 0.05.


RESULTS
Seventeen percent (17/100) of H. pylori-infected MGs developed gastric cancer. All of these lesions were well-differentiated adenocarcinoma. The incidence rates of adenocarcinoma in groups A-F were 40%, 0%, 0%, 20%, 25%, and 0% respectively. The inflammatory scores were higher in group B than in other groups. There was no inflammatory response noted in group F. Celecoxib treatment resulted in a significant reduction in the proliferation of H. pylori-infected mucosal cells (groups B, C and D) (P < 0.01). The expression of COX-2 protein was significantly attenuated in the groups which were celecoxib-treated for more than 20 wk (groups B, C, D). The groups treated with celecoxib had a significantly lower rate of advanced gastric cancer (34% vs 75%, P < 0.001) There were no sudden deaths in any of the groups.


CONCLUSIONS
Short-term treatment with celecoxib has an anti-carcinogenic effect, and resulted in less severe inflammation and inhibited the invasive degree of gastric cancer.
Division of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung 813, Taiwan, China.
Chao-Hung
CH
Kuo
Huang-Ming
HM
Hu
Pei-Yun
PY
Tsai
I-Chen
IC
Wu
Sheau-Fang
SF
Yang
Lin-Li
LL
Chang
Jaw-Yuan
JY
Wang
Chang-Ming
CM
Jan
Wen-Ming
WM
Wang
Deng-Chyang
DC
Wu
D000230:Adenocarcinoma / Q000139:chemically induced / Q000201:enzymology / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage*; D000068579:Celecoxib; D049109:Cell Proliferation / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005753:Gastric Mucosa / Q000187:drug effects* / Q000201:enzymology / Q000382:microbiology / Q000473:pathology; D005849:Gerbillinae; D016480:Helicobacter pylori / Q000472:pathogenicity; D008769:Methylnitronitrosoguanidine; D009361:Neoplasm Invasiveness; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011720:Pyrazoles / Q000008:administration & dosage*; D013274:Stomach Neoplasms / Q000139:chemically induced / Q000201:enzymology / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control*; D013449:Sulfonamides / Q000008:administration & dosage*; D013997:Time Factors
D016588:Anticarcinogenic Agents; D052246:Cyclooxygenase 2 Inhibitors; D018809:Proliferating Cell Nuclear Antigen; D011720:Pyrazoles; D013449:Sulfonamides; D008769:Methylnitronitrosoguanidine; D051546:Cyclooxygenase 2; D000068579:Celecoxib