组织缺氧诱导因子-1α及相关靶基因在喉鳞状细胞癌组织中的表达

Expression of hypoxia inducible factor-1α and correlated target genes in human laryngeal carcinoma

目的检测喉鳞状细胞癌（简称鳞癌）组织缺氧诱导因子-1α（hypoxia inducible factor 1 alpha，HIF-1α）、葡萄糖转运蛋白-1（glucose transporter protein-1，GLUT-1）、血管内皮生长因子（vascular endothelial growth factor，VEGF）的蛋白表达情况，并通过体外实验进一步验证低氧对喉鳞癌细胞HIF—1α及其下游靶基因GLUT-1、VEGF的表达上调方面的重要促进作用。方法采用SP免疫组织化学和免疫细胞化学方法检测喉鳞癌组织和Hep-2细胞中HIF-1α、GLUT-1、VEGF蛋白的表达，分析HIF-1α与GLUT—1、VEGF表达的相关性。结果35例喉癌患者组织切片中16例HIF-1α表达阳性（45．7％），16例GLUT-1表达阳性（阳性率45．7％），19例VEGF表达阳性（阳性率54．3％）。HIF-1α和VEGF的表达水平与喉癌病理分级和淋巴转移有关（P值均〈0．05）；GLUT-1表达水平与淋巴转移有关（P〈0．05）。体外实验结果显示，Hep-2细胞在低氧条件下HIF-1α、GLUT-1、VEGF的蛋白表达明显增加（P值均〈0．05）。结论HIF-1α可作为转录调控因子参与调控GLUT-1、VEGF的表达，进而在喉癌的发生、侵袭、转移过程中发挥重要作用。

Objective To detect the expression of hypoxia inducible factor 1 alpha （HIF-1α）, glucose transporter protein-1 （GLUT-1） and vascular endothelial growth factor （VEGF） in human laryngeal carcinoma tissue, and to study the relationship between hypoxia and HIF-1α, GLUT-1, VEGF in human laryngeal carcinoma Hep-2 cells and to explore the effect of HIF-1α, GLUT-1 and VEGF as endogenous hypoxic markers on laryngeal carcinoma. Methods The expression levels of HIF-1α, GLUT-1 and VEGF were detected in 35 cases of laryngeal carcinoma by SP immunohistochemical methods and in Hep-2 cells by SP immunocytochemical methods. The relationship between HIF-1α and GLUT-1, VEGF protein expression was analyzed. Results Of the 35 cases, 16 cases expressed HIF-1α, 16 cases expressed GLUT-1, 19 cases expressed VEGF. The expression of HIF-1 ct and VEGF were closely correlated with pathologic grading and lymphnode metastasis. GLUT-1 was correlated with lymphnode metastasis. The expression levels of HIF- la, GLUT-1 and VEGF in Hep-2 cells under hypoxic condition were higher than those under normoxic condition. Conclusion HIF1α may promote the expression of GLUT-1 and VEGF in laryngeal carcinoma, furthermore promote tumor angiogenesis, invasion, and metastasis of the laryngeal carcinoma.