Chemoprevention of esophageal adenocarcinoma by COX-2 inhibitors in an animal model of Barrett's esophagus
Chemoprevention of esophageal adenocarcinoma by COX-2 inhibitors in an animal model of Barrett's esophagus
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DOI：
10.1053/gast.2002.32371
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发表时间：
2002-04-01
期刊：
影响因子：
29.4
通讯作者：
Burgart, LJ
中科院分区：
文献类型：
--
作者：
Buttar, NS;Wang, KK;Burgart, LJ
背景与目的：Barrett食管（BE）的癌变与环氧合酶（考克斯）2表达增加有关。然而，没有直接证据表明抑制考克斯-2可以预防BE中的癌症。我们研究了选择性考克斯-2抑制剂MF-Tricyclic对大鼠BE和腺癌发展的影响。方法：食管空肠吻合术后4周，将105只Sprague-Dawley大鼠随机分配至含MF-三环或舒林酸或安慰剂的饲料中。96只（92%）大鼠完成研究，并在28 +/- 2周时处死。评估动物是否存在癌症、肿瘤体积、BE、炎症程度以及考克斯-2表达和活性。结果如下：与对照组相比，MF-三环和舒林酸分别使食管癌发生的相对风险降低了55%（95%置信区间[C1] = 43%-66%，P < 0.008）和79%（95% CI = 68%-87%，P < 0.001）。MF-三环类和舒林酸组之间的食管癌风险无显著差异（P = 0.34）。中位肿瘤体积在3组之间无显著差异（P = 0.081）。与MF-三环类和舒林酸组相比，对照组中中度至重度炎症明显更常见（P = 0.005）;然而，两组间BE的患病率无显著差异（P = 0.98）。对照组大鼠的组织PGE（2）水平高于MF-三环和舒林酸组（P = 0.038）。结论：选择性和非选择性考克斯-2抑制剂可以抑制炎症、考克斯-2活性和由反流诱导的腺癌的发展。这为考克斯-2抑制剂可能对BE具有化学预防潜力提供了直接证据。
Background & Aims: Carcinogenesis in Barrett's esophagus (BE) is associated with an increased expression of cyclooxygenase (COX) 2. However, there has been no direct evidence that inhibition of COX-2 prevents cancer in BE. We studied the effect of MF-Tricyclic, a selective COX-2 inhibitor, on the development of BE and adenocarcinoma in a rat model. Methods: Four weeks after esophagojejunostomy, :105 Sprague-Dawley rats were randomized to a chow containing MF-Tricyclic or Sulindac, or a placebo. Ninety-six (92%) rats completed the study and were sacrificed at 28 +/- 2 weeks. The animals were assessed for the presence of cancer, tumor volume, BE, degree of inflammation, and COX-2 expression and activity. Results : MF-Tricyclic and Sulindac reduced the relative risk of development of esophageal cancer by 55% (95% confidence interval [C1] = 43%-66%, P < 0.008) and by 79% (95% Cl = 68%-87%, P < 0.001), respectively, compared with controls. No significant differences were noted in the risk of esophageal cancer between the MF-Tricyclic and the Sulindac group (P = 0.34). The median tumor volume was not significantly different among the 3 groups (P = 0.081). Moderate to severe degree of inflammation was significantly more common (P = 0.005) in the control compared with the MF-Tricyclic and the Sulindac group; however, the prevalence of BE was not significantly different between groups (P = 0.98). Rats in the control group had higher tissue PGE(2) level compared with the MF-Tricyclic and Sulindac groups (P = 0,038). Conclusions: Selective and nonselective COX-2 inhibitors can inhibit inflammation, COX-2 activity, and development of adenocarcinoma induced by reflux. This provides direct evidence that COX-2 inhibitors may have chemopreventive potential in BE.