Up-regulation of cyclooxygenase 2 gene expression correlates with tumor angiogenesis in human colorectal cancer
Up-regulation of cyclooxygenase 2 gene expression correlates with tumor angiogenesis in human colorectal cancer
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DOI：
10.1053/gast.2001.29691
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发表时间：
2001-12-01
期刊：
影响因子：
29.4
通讯作者：
Masini, E
中科院分区：
文献类型：
--
作者：
Cianchi, F;Cortesini, C;Masini, E
背景和目标：近年来的研究表明，环氧合酶（考克斯）-2及其产物前列腺素（PGs）可能参与结直肠癌的发生。本研究的目的是确定考克斯-2表达和PGE（2）的产生是否与人结直肠癌中微血管密度、血管内皮生长因子（VEGF）表达和肿瘤转移相关。方法：31例手术切除的肿瘤标本及癌旁正常粘膜标本。免疫组化分析石蜡包埋组织切片中考克斯-2、VEGF和CD 31的表达。Western blot法检测考克斯-2和考克斯-1蛋白的表达。采用北方印迹法检测考克斯-2和VEGF mRNA的表达。用放射免疫法测定PGE（2）的产生。结果如下：考克斯-2和VEGF的表达与微血管密度显著相关（P = 0.02和P = 0.002）。考克斯-2与VEGF的表达有显著相关性（P = 0.004）。Western分析证实考克斯-2蛋白表达上调。考克斯-2和VEGF基因在肿瘤组织中的表达明显高于正常黏膜组织。转移瘤组PGE（2）水平明显高于非转移瘤组（P = 0.03）。结论：考克斯-2与大肠癌血管生成有关。VEGF可能是考克斯-2血管生成途径中最重要的介质之一。
Background & Aims: Recent studies have shown that cyclooxygenase (COX)-2 and its products, prostaglandins (PGs), may be involved in colorectal carcinogenesis. The aim of this study was to determine whether COX-2 expression and PGE(2) production correlate with microvessel density, vascular endothelial growth factor (VEGF) expression, and tumor metastasis in human colorectal cancer. Methods: Tumor samples and adjacent normal mucosa were obtained from 31 surgical specimens. Immunohistochemical expression of COX-2, VEGF, and CD31 was analyzed on paraffin-embedded tissue sections. COX-2 and COX-1 proteins were determined by Western blot analysis. COX-2 and VEGF messenger RNA expressions were evaluated using Northern blot analysis. PGE(2) production was determined by specific radioimmunoassay. Results: The immunohistochemical expressions of both COX-2 and VEGF were significantly correlated with microvessel density (P = 0.02 and P = 0.002, respectively). A significant correlation was found between COX-2 and VEGF expression (P = 0.004). Western analysis confirmed the up-regulation of COX-2 protein expression. COX-2 and VEGF genes were overexpressed in tumor specimens as compared with normal mucosa. PGE(2) levels were significantly higher in metastatic tumors than in nonmetastatic ones (P = 0.03). Conclusions: COX-2 is related to tumor angiogenesis in colorectal cancer. It is likely that VEGF is one of the most important mediators of the COX-2 angiogenic pathway.