title: Chemoprevention of esophageal adenocarcinoma in a rat model by ursodeoxycholic acid.
abstract: Reflux of bile acid into the esophagus induces esophagitis, inflammation-stimulated hyperplasia, metaplasia such as Barrett's esophagus (BE), and esophageal adenocarcinoma (EAC). Caudal-type homeobox 2 (Cdx2) via nuclear factor (NF)-κB induced by bile acid is an important factor in the development of BE and EAC. In colorectal cancer, experimental data suggest a chemopreventive effect of ursodeoxycholic acid (UDCA). We hypothesized that UDCA may protect against the esophageal inflammation-metaplasia-carcinoma sequence by decreasing the overall proportion of the toxic bile acids. Wistar male rats that underwent a duodenoesophageal reflux procedure were divided into two groups. One group was given commercial chow (control group), and the other was given experimental chow containing UDCA (UDCA group). The animals were killed at 40 weeks after surgery, and their bile and esophagus were examined. In the UDCA group, the esophagitis was milder and the incidence of BE was significantly lower (p < 0.05) than in the control group, and EAC was not observed (p < 0.05). In analysis of the compartment of bile acid, UDCA was markedly increased in the UDCA group compared with the control group (32.7 ± 11.4 vs. 0.82 ± 0.33 mmol/L, p < 0.05) and cholic acid was decreased (32.7 ± 4.05 vs. 60.9 ± 8.26 mmol/L, p < 0.05). Expression intensity of Cdx2 and NF-κB was greater in the control group than in the UDCA group (p < 0.05). UDCA may be a chemopreventive agent against EAC by varying the bile acid composition.
authors.affiliation: Department of Gastroenterologic Surgery, Kanazawa University, 13-1, Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan.
authors.forename: Eisuke
authors.initials: E
authors.lastname: Ojima
authors.forename: Takashi
authors.initials: T
authors.lastname: Fujimura
authors.forename: Katsunobu
authors.initials: K
authors.lastname: Oyama
authors.forename: Tomoya
authors.initials: T
authors.lastname: Tsukada
authors.forename: Jun
authors.initials: J
authors.lastname: Kinoshita
authors.forename: Tomoharu
authors.initials: T
authors.lastname: Miyashita
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Tajima
authors.forename: Sachio
authors.initials: S
authors.lastname: Fushida
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Harada
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Mukaisho
authors.forename: Takanori
authors.initials: T
authors.lastname: Hattori
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Ohta
mesh_terms: D000230:Adenocarcinoma / Q000517:prevention & control*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D000071616:CDX2 Transcription Factor; D018890:Chemoprevention / Q000379:methods*; D004195:Disease Models, Animal; D004938:Esophageal Neoplasms / Q000517:prevention & control*; D004947:Esophagus / Q000473:pathology; D020869:Gene Expression Profiling; D006651:Histocytochemistry; D018398:Homeodomain Proteins / Q000032:analysis; D007150:Immunohistochemistry; D008297:Male; D008853:Microscopy; D016328:NF-kappa B / Q000032:analysis; D017208:Rats, Wistar; D014157:Transcription Factors / Q000032:analysis; D016896:Treatment Outcome; D014580:Ursodeoxycholic Acid / Q000008:administration & dosage*
chemical_list: D000970:Antineoplastic Agents; D000071616:CDX2 Transcription Factor; C541055:Cdx2 protein, rat; D018398:Homeodomain Proteins; D016328:NF-kappa B; D014157:Transcription Factors; D014580:Ursodeoxycholic Acid