Sulindac prevents esophageal adenocarcinomas induced by gastroduodenal reflux in rats.
OBJECTIVE
It is known that cyclooxygenase (COX)-2 expression is increased in Barrett's esophagus and esophageal adenocarcinomas. We studied COX-2 expression and the effect sulindac has on the genesis of Barrett's esophagus and adenocarcinoma in rats undergoing esophagogastroduodenal anastomosis (EGDA).


METHODS
Fifty-one rats were divided into a control group (n=27), a 500 ppm sulindac-treated group (n=15) and 1000 ppm sulindac-treated group (n=9). Randomly selected rats were killed by diethyl ether inhalation at 20 and 40 weeks after surgery.


RESULTS
At 40 weeks, rats treated with 1000 ppm sulindac showed narrower esophageal diameter and milder inflammation than the control rats. At 40 weeks, the incidence of Barrett's esophagus was similar between control and sulindac-treated groups, but the incidence of adenocarcinoma was significantly lower in the 1000 ppm sulindac-treated group than either the control or 500 ppm sulindac-treated groups. COX-2 was significantly increased in the lower esophagus of control rats killed at 40 weeks. Cyclin D1 expression was negligible in the sulindac- treated group compared with the control group.


CONCLUSIONS
We suggest that the chemopreventive effect of sulindac is related to decreased COX-2 and cyclin D1 expression, which may be influenced by reduced inflammation.
Kim
Sung Wook
SW
Departments of Gastroenterology, Dongguk University College of Medicine, Kyongju, Korea.
Jang
Tae Jung
TJ
Jung
Ki Hoon
KH
Suh
Jung Il
JI
D000230:Adenocarcinoma / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001471:Barrett Esophagus / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D015153:Blotting, Western; D019938:Cyclin D1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004383:Duodenogastric Reflux / Q000150:complications*; D004938:Esophageal Neoplasms / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D007150:Immunohistochemistry; D008297:Male; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013467:Sulindac / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D018809:Proliferating Cell Nuclear Antigen; D019938:Cyclin D1; D013467:Sulindac; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human