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A selective cyclooxygenase-2 inhibitor (Etodolac) prevents spontaneous biliary tumorigenesis in a hamster
Amane Kitasato1, Tamotsu Kuroki, Tomohiko Adachi
1Department of Surgery, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
Background:
Secondary biliary carcinomas are associated with persistent reflux cholangitis after bilioenterostomy. Cyclooxygenase-2 (COX-2) has been a target for cancer prevention. The aim of this study was to evaluate the chemopreventive efficacy of long-term treatment with a selective COX-2 inhibitor medication during the natural course after bilioenterostomy without chemical induction.
Methods:
Syrian golden hamsters which underwent choledochojejunostomy were randomly divided into two groups: the control group (n = 31), which was fed a normal diet, and the etodolac group (n = 33), which was fed 0.01% etodolac (a selective COX-2 inhibitor) mixed in the meal. The hamsters were killed at the postoperative weeks 20-39, 40-59, 60-79, or 80-100. Biliary neoplasms, cholangitis, proliferating cell nuclear antigen labeling index (PCNA-LI) of the biliary epithelium, and prostaglandin E2 (PGE2) production were evaluated.
Results:
The occurrence rates of biliary neoplasm were 43.8 and 15.2% in the control and etodolac groups, respectively (p < 0.05). The incidence of biliary neoplasm increased as time progressed in the control group, whereas it remained at a low level throughout the experimental period in the etodolac group. PGE2 products tended to be lower in the etodolac group, and PCNA-LI was significantly lower in the etodolac group (p < 0.01). These results suggest that the medication etodolac suppresses cell proliferation of the biliary epithelium, thereby preventing biliary carcinogenesis.
Conclusions:
Etodolac is expected to prevent secondary biliary carcinogenesis caused by persistent reflux cholangitis after bilioenterostomy.
Insights
Long-term use of etodolac, a selective cyclooxygenase-2 (COX-2) inhibitor, significantly reduced the incidence of biliary neoplasms in hamsters with secondary biliary carcinogenesis. This suggests etodolac may prevent cancer development linked to persistent cholangitis.
Area of Science:
- Gastroenterology
- Oncology
- Pharmacology
Background:
- Secondary biliary carcinomas are linked to persistent reflux cholangitis post-bilioenterostomy.
- Cyclooxygenase-2 (COX-2) is a known target for cancer prevention strategies.
- This study investigated the chemopreventive potential of a COX-2 inhibitor in a natural disease course model.
Purpose of the Study:
- To evaluate the chemopreventive efficacy of long-term etodolac treatment.
- To assess the impact of etodolac on biliary carcinogenesis after bilioenterostomy.
- To examine the effects on cholangitis, cell proliferation, and prostaglandin E2 production.
Main Methods:
- Syrian golden hamsters underwent choledochojejunostomy and were divided into control and etodolac groups.
- The etodolac group received 0.01% etodolac in their diet for up to 100 weeks.
- Evaluated biliary neoplasms, cholangitis, PCNA-LI, and PGE2 production.
Main Results:
- Biliary neoplasm occurrence was significantly lower in the etodolac group (15.2%) compared to controls (43.8%).
- Etodolac treatment maintained a low incidence of biliary neoplasms throughout the study.
- Prostaglandin E2 (PGE2) levels and proliferating cell nuclear antigen labeling index (PCNA-LI) were significantly reduced in the etodolac group.
Conclusions:
- Etodolac demonstrates chemopreventive efficacy against secondary biliary carcinogenesis.
- The medication suppresses biliary epithelial cell proliferation, thereby preventing cancer development.
- Etodolac is a potential therapeutic agent for preventing biliary cancers associated with reflux cholangitis.
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