Increased cyclooxygenase-2 levels in carcinogen-induced rat colonic tumors
Increased cyclooxygenase-2 levels in carcinogen-induced rat colonic tumors
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DOI：
10.1053/gast.1996.v110.pm8613017
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发表时间：
1996-04-01
期刊：
影响因子：
29.4
通讯作者：
Entingh, AJ
中科院分区：
文献类型：
--
作者：
DuBois, RN;Radhika, A;Entingh, AJ
背景和目标：多项研究表明，持续使用非甾体抗炎药（NSAID）可降低人类和致癌物治疗的啮齿动物患结肠癌的风险。NSAID的一个靶点是环氧合酶（考克斯），并且已经鉴定了该酶的两种同种型：考克斯-1和考克斯-2。本研究旨在确定氧化偶氮甲烷处理大鼠结肠肿瘤中是否存在考克斯的差异表达。研究方法：北方印迹分析从结肠肿瘤和正常邻近粘膜中分离的总RNA，测定考克斯-1和考克斯-2信使RNA水平。Western blotting法检测考克斯-2蛋白表达。使用标准光密度扫描技术进行相对条带密度的定量。结果：6例结肠肿瘤组织中考克斯-2 RNA表达水平明显高于正常结肠组织。相反，在所有检查的标本中，正常粘膜和肿瘤之间的考克斯-1 RNA转录物的强度相等。Western印迹分析显示，在5个结肠肿瘤样本中的4个中，考克斯-2蛋白水平增加。结论：考克斯-2，而不是考克斯-1基因表达显着升高，在大多数结肠肿瘤检查氧化偶氮甲烷治疗啮齿动物。考克斯-2可能为结直肠癌的化学预防策略提供一个靶点。
Background & Aims: Multiple studies show that continuous use of nonsteroidal anti-inflammatory drugs (NSAIDs) lowers the risk of colon cancer in humans and carcinogen-treated rodents. One target for NSAIDs is cyclooxygenase (COX), and two isoforms of this enzyme have been identified: COX-1 and COX-2. The present study was undertaken to determine if there is differential expression of COX in colonic tumors in azoxymethane-treated rats. Methods: COX-1 and COX-2 messenger RNA levels were determined by Northern blot analysis of total RNA isolated from colonic tumors and normal adjacent mucosa. COX-2 protein levels were determined by Western blotting analysis. Quantitation of relative band densities was performed using standard densitometry scanning techniques. Results: There was a marked increase in COX-2 RNA levels in six of six of the colonic tumors compared with paired normal mucosa. In contrast, there was equivalent intensity of the COX-1 RNA transcript between the normal mucosa and tumor in all of the specimens examined. Western blotting analysis showed an increase in the level of the COX-2 protein in four of five of the colonic tumor samples. Conclusions: COX-2 but not COX-1 gene expression is markedly elevated in most colonic tumors examined in azoxymethane-treated rodents. COX-2 may provide a target for chemopreventive strategies for colorectal cancer.