缺氧诱导因子-1α和血管内皮生长因子在人大肠癌中的表达水平及意义

Expression levels and significance of hypoxia inducible factor-1 alpha and vascular endothelial growth factor in human colorectal adenocarcinoma.

作者信息

Jiang Cong-qing, Fan Li-fang, Liu Zhi-su, Qian Qun, Xia Dong, Diao Lu-ming, He Yue-ming, Ai Zhong-li

机构信息

Department of Colorectal Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.

出版信息

Chin Med J (Engl). 2004 Oct;117(10):1541-6.

PMID:15498380

Abstract

BACKGROUND

Hypoxia-inducible factor 1 (HIF-1), a transcription factor, is overexpressed in common human cancers and their metastases. This study aimed at determining the expression levels of HIF-1alpha and vascular endothelial growth factor (VEGF) in SW480 cells and in colorectal adenocarcinoma tissue and ascertaining whether HIF-1alpha and VEGF play important roles in tumor angiogenesis.

METHODS

HIF-1alpha mRNA expression was analyzed using in situ hybridization and RT-PCR. HIF-1alpha and VEGF protein were detected in SW480 cells and colorectal adenomas and adenocarcinomas by immunohistochemistry using streptavidin/peroxidase (SP). Western blot was used to detect HIF-1alpha protein extracted from SW480 cells. Microvessel density (MVD) in colorectal carcinomas was determined by anti-CD34 immunostaining in colorectal carcinomas.

RESULTS

Optical density values representing HIF-1alpha mRNA expression levels were found to be significantly higher in SW480 cells in hypoxic conditions than in cells under normoxic conditions (P < 0.05) or in hypoxic conditions but treated with genistein (P < 0.05). The levels of HIF-1alpha and VEGF protein expression in SW480 cells were significantly higher in the hypoxia group than in the normoxia group (P < 0.01, P < 0.05, respectively) and hypoxia/genistein group (P < 0.01, P < 0.05, respectively). The positive expression rates of HIF-1alpha mRNA changed dramatically when comparing colorectal adenomas with adenocarcinomas of different Dukes' stages (P < 0.05). HIF-1alpha mRNA was also expressed at higher levels in adenocarcinomas than that in adenomas (P < 0.01). HIF-1alpha protein expression correlated significantly with VEGF protein expression and MVD.

CONCLUSIONS

Hypoxia induces the expression of HIF-1alpha and VEGF in colorectal adenocarcinomas. HIF-1alpha may play an important role in angiogenesis and tumor progression by regulating the expression of VEGF in human colorectal carcinomas.

摘要

背景

缺氧诱导因子1（HIF-1）作为一种转录因子，在常见人类癌症及其转移灶中呈过表达。本研究旨在测定HIF-1α和血管内皮生长因子（VEGF）在SW480细胞及结直肠癌组织中的表达水平，并确定HIF-1α和VEGF在肿瘤血管生成中是否发挥重要作用。

方法

采用原位杂交和逆转录-聚合酶链反应（RT-PCR）分析HIF-1α mRNA的表达。利用链霉亲和素/过氧化物酶（SP）免疫组织化学法检测SW480细胞、结直肠腺瘤及腺癌中的HIF-1α和VEGF蛋白。采用蛋白质印迹法检测从SW480细胞中提取的HIF-1α蛋白。通过抗CD34免疫染色测定结直肠癌中的微血管密度（MVD）。

结果

发现缺氧条件下SW480细胞中代表HIF-1α mRNA表达水平的光密度值显著高于常氧条件下的细胞（P<0.05）或缺氧但用染料木黄酮处理的细胞（P<0.05）。缺氧组SW480细胞中HIF-1α和VEGF蛋白表达水平显著高于常氧组（分别为P<0.01，P<0.05）和缺氧/染料木黄酮组（分别为P<0.01，P<0.05）。比较不同Dukes分期的结直肠腺瘤与腺癌时，HIF-1α mRNA的阳性表达率变化显著（P<0.05）。腺癌中HIF-1α mRNA的表达水平也高于腺瘤（P<0.01）。HIF-1α蛋白表达与VEGF蛋白表达及MVD显著相关。