Cyclooxygenase-2 expression in hamster and human pancreatic neoplasia
Cyclooxygenase-2 expression in hamster and human pancreatic neoplasia
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DOI：
10.1593/neo.04700
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发表时间：
2006-06-01
期刊：
影响因子：
4.8
通讯作者：
Cummings, William O.
中科院分区：
文献类型：
--
作者：
Crowell, Pamela L.;Schmidt, C. Max;Cummings, William O.
环氧合酶-2（考克斯-2）与胃肠道恶性肿瘤的发生发展有关。本研究的目的是确定考克斯-2的表达/活性在整个阶段的实验和人类胰腺肿瘤。在接触致癌物N-亚硝基双-（2-氧代丙基）胺（BOP）的仓鼠胰腺和人类胰腺肿瘤中进行了考克斯-2免疫组织化学研究。采用前列腺素E-2法检测肿瘤组织和正常胰腺组织中的考克斯-2活性。在PC-1仓鼠胰腺癌模型中测试考克斯抑制剂舒林酸的活性。考克斯-2表达在所有胰腺上皮内瘤变（PanIN）和腺癌中均升高。在BOP处理的仓鼠中，在胰腺肿瘤发生的整个过程中，考克斯-2表达显著进行性升高。在人类样本中，考克斯-2表达峰值出现在PanIN 2病变中，并在PanIN 3和腺癌组织中保持适度升高。与配对的正常胰腺相比，仓鼠和人胰腺癌中的考克斯-2活性显著升高。此外，通过口服舒林酸，PC-1仓鼠胰腺癌模型中的仓鼠胰腺肿瘤植入/形成减少了4.9倍。考克斯-2表达增加是胰腺癌发生的早期事件。BOP诱导的仓鼠癌发生模型是用于研究考克斯-2在高分化胰腺肿瘤发生中的作用的代表性模型。考克斯抑制剂可能在预防肿瘤植入/形成中起作用。
Cyclooxygenase-2 (COX-2) has been implicated in the development of gastrointestinal malignancies. The aim of the present study was to determine COX-2 expression/activity throughout stages of experimental and human pancreatic neoplasia. COX-2 immunohistochemistry was performed in pancreata of hamsters subjected to the carcinogen N-nitrosobis-(2-oxopropyl) amine (BOP) and in human pancreatic tumors. COX-2 activity was determined by prostaglandin E-2 assay in tumor versus matched normal pancreatic tissues. The activity of the COX inhibitor sulindac was tested in the PC-1 hamster pancreatic cancer model. COX-2 expression was elevated in all pancreatic intra-epithelial neoplasias (PanINs) and adenocarcinomas. In BOP-treated hamsters, there were significant progressive elevations in COX-2 expression throughout pancreatic tumorigenesis. In human samples, peak COX-2 expression occurred in PanIN2 lesions and remained moderately elevated in PanIN3 and adenocarcinoma tissues. COX-2 activity was significantly elevated in hamster and human pancreatic cancers compared to pair-matched normal pancreas. Furthermore, hamster pancreatic tumor engraftment/formation in the PC-1 hamster pancreatic cancer model was reduced 4.9-fold by oral administration of sulindac. Increased COX-2 expression is an early event in pancreatic carcinogeneses. The BOP-induced hamster carcinogenesis model is a representative model used to study the role of COX-2 in well-differentiated pancreatic tumorigenesis. COX inhibitors may have a role in preventing tumor engraftment/formation.