Zhang Tao, Su Li-wei, Zhu Yi-fang, Lang Hong-juan, Zhang Feng, Zhou Yong-an, Liang Xiao-hua, Wang Yun-jie
Department of Thoracic Surgery, The Fourth Military Medical University, Xi'an, China.
Zhonghua Wei Chang Wai Ke Za Zhi. 2012 May;15(5):512-6.
To study the feasibility of chemoprevention of esophageal adenocarcinoma by celecoxib, a selective cyclooxygenase-2(COX-2) inhibitor using a rat model.
Rats were divided into 3 groups: model group, celecoxib group, and control group. The rat surgical model was established by performing a gastrojejunostomy plus an esophagojejunostomy 5 mm distal to the gastrojejunal anastomosis. Twenty-eight weeks after surgery, all the animals were sacrificed and the pathological changes in the esophagus were examined macroscopically. COX-2 expression was analyzed by immunohistochemistry. Prostaglandin E2(PGE2) level was measured by enzyme-linked immunosorbent assay(ELISA).
The incidence of Barrett's esophagus and esophageal adenocarcinoma in the model group was 84% and 57% respectively, significantly higher than those in the control group(P<0.01). The incidence of esophageal adenocarcinoma in the celecoxib-treated group was significantly lower than that in the model group(P<0.01), and no esophageal adenocarcinoma was detected in the control group. COX-2 expression was detected in 100% of reflux esophagitis, Barrett esophagus and esophageal adenocarcinoma, but not found in the normal tissue from the esophagus and the jejunum(P<0.01). The PGE2 level in the esophageal tissue in the model group was significantly higher than that in the control group(P<0.01). Rats in the celecoxib-treated group had significantly lower PGE2 level than that in the model group(P<0.01). The PGE2 levels were significantly higher in rats with cancer than those without cancer(P<0.01).
Celecoxib successfully prevents the development of esophageal adenocarcinoma in a rat surgical model with mixed reflux of acid and duodenal juice and significantly decreases the risk of Barrett esophagus developing esophageal adenocarcinoma. COX-2 maybe an effective selective target of chemoprevention for esophageal adenocarcinoma.
使用大鼠模型研究选择性环氧化酶-2（COX-2）抑制剂塞来昔布对食管腺癌进行化学预防的可行性。
将大鼠分为3组：模型组、塞来昔布组和对照组。通过进行胃空肠吻合术并在胃空肠吻合口远端5毫米处进行食管空肠吻合术建立大鼠手术模型。术后28周，处死所有动物，大体检查食管的病理变化。通过免疫组织化学分析COX-2表达。采用酶联免疫吸附测定（ELISA）法测定前列腺素E2（PGE2）水平。
模型组巴雷特食管和食管腺癌的发生率分别为84%和57%，显著高于对照组（P<0.01）。塞来昔布治疗组食管腺癌的发生率显著低于模型组（P<0.01），对照组未检测到食管腺癌。100%的反流性食管炎、巴雷特食管和食管腺癌中检测到COX-2表达，但在食管和空肠的正常组织中未发现（P<0.01）。模型组食管组织中的PGE2水平显著高于对照组（P<0.01）。塞来昔布治疗组大鼠的PGE2水平显著低于模型组（P<0.01）。有癌大鼠的PGE2水平显著高于无癌大鼠（P<0.01）。
塞来昔布成功预防了酸和十二指肠液混合反流的大鼠手术模型中食管腺癌的发生，并显著降低了巴雷特食管发展为食管腺癌的风险。COX-2可能是食管腺癌化学预防的有效选择性靶点。
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