肝癌组织中缺氧与血管内皮生长因子过度表达的关系

Relationshib between overexpression of vascular endothelial growth factor and hypoxia in hepatocellular carcinoma

目的 研究肝细胞癌 (HCC)中血管内皮生长因子 (VEGF)过度表达与HCC组织中缺氧的关系。方法 通过免疫组织化学链霉亲合素 生物素 过氧化物酶复合体 (SABC)法检测 3 6例HCC组织及其相应癌旁肝组织和 6例正常肝组织中缺氧诱生因子 1α(HIF 1α)、VEGF和微血管密度(MVD)的表达 ,并对这些指标进行相关分析。离体实验中用缺氧诱导剂氯化钴刺激人肝癌细胞系HepG2 ,采用半定量逆转录 聚合酶链反应 (RT PCR)和免疫组织化学检测VEGF的表达情况。结果 3 6例HCC组织中HIF 1α强阳性 3例 (8.3 % )、弱阳性 2 1例 (5 8.3 % )、阴性 12例 (3 3 .3 % ) ;VEGF强阳性 16例 (4 4 .4% )、弱阳性 16例 (4 4 .4% )、阴性 4例 (12 .2 % )。等级相关分析显示HCC中VEGF的表达与MVD的表达、HIF 1α的表达与VEGF的表达均具有正相关关系 (P <0 .0 1)。氯化钴可以以浓度和时间依赖性的方式诱导HepG2细胞中VEGF的转录。结论 HCC中存在的缺氧是HCC组织中VEGF过度表达的始动因素之一。

ObjectiveTo investigate the relationship between overexpression of vascular endothelial growth factor (VEGF) and hypoxia in hepatocellular carcinoma (HCC).MethodsThe expression of hypoxia-inducible factor 1 alpha (HIF-1α),VEGF and microvessel density (MVD) were studied through immunohistochemistry in 36 cases of HCC and their paraneoplastic tissue and 6 cases of normal liver tissue.The relationship between these parameters were analyzed.The expression of VEGF was detected by using semi-quantitative reverse transcriptional polymerase chain reaction and immunocytochemistry.The levels of VEGF expression were compared between non-stimulated and cobalt chloride-stimulated HepG2.ResultsIn HCC group,strong expression of HIF-1α was detected in 3 (8.3%) specimens,weak in 21 (58.3%),and no expression in 12 samples (33.3%);Strong expression of VEGF was observed in 16 (44.4%) specimens,weak in 16 (44.4%),and no expression in 4 samples (12.2%).There was a close correlation between VEGF expression and MVD ( P <0.01).The HIF-1α expression and VEGF also showed a strong correlation ( P <0.01).Cobalt chloride could stimulate the expression of VEGF mRNA in a time-and concentration-dependent manner.ConclusionVEGF overexpression could be promoted primarily by hypoxia in HCC.