UNC5b基因表达下调与肝细胞癌血管生成的关系

目的 探讨UNC5b基因在肝细胞癌(HCC)血管生成中的作用.方法 收集中南大学湘雅医院外科2004年10月至2005年8月期间手术切除并经病理确诊为HCC的肿瘤标本和相应距瘤体1 cm外的癌旁肝组织各38例,另取5例正常肝组织作为对照.采用组织原位杂交的方法检测UNC5b mRNA在HCC组织、痛旁组织以及正常肝组织中的表达情况,并分析其与HCC临床病理特征之间的关系.分离培养人脐动脉内皮细胞(HUAEC),用HCC组织匀浆及血管内皮生长因子(VEGF)、碱性成纤维细胞生长因子(bFGF)联合刺激活化HUAEC,应用RT-PGR方法分析其活化前后UNC5b基因的表达水平.结果 原位杂交结果显示,UNC5b主要表达于正常肝组织以及部分癌旁组织的血管内皮细胞胞质中;在HCC组织的血管内皮细胞中呈弱表达或不表达;HCC组织内皮细胞中UNC5b的表达强弱与肿瘤分化程度、肿瘤结节的数目、肿瘤大小、有无包膜、肝硬化程度无相关性(P>0.05);癌旁组织内皮细胞中UNC5b的表达与有无包膜显著相关(P=0.003).UNC5b基因在未活化的HUAEC中呈强表达(0.973±0.012),在联合刺激活化后的HUAEC中表达明显下调(0.451±0.113,P<0.05).结论 UNC5b基因在HCC组织血管内皮细胞及活化后的HUAEC中的表达均明显下调,提示UNC5b的表达下调可能与HCC的血管生成相关.

Down-regulated expression of UNC5b related to hepatocellular carcinoma angiogenesis

Objective To investigate the relationship between UNC5b gene expression and angiogenesis of hepatocellular carcinoma (HCC). Methods In situ hybridization was performed to detect the expression of UNC5b mRNA in HCC samples, paracarcinomatous liver tissues samples and normal liver samples. The relationship between UNC5b mRNA expression and the HCC clinicopathological features were also analyzed. Human umbilical arter endothelial cells were isolated and stimulated with HCC tissues homogenate, vascular endothelial growth factor and basic fibroblast growth factor. Then RT-PCR was employed to detect the expression of UNC5b mRNA in normal HUAEC as well as activated HUAEC. Results In situ hybridization results showed that UNC5b mRNA expression was detected majorly in endothelial cells of all normal liver tissues, and partial PCLTs but was weak or even undetectable in endothelial cells of the corresponding HCC tissues, The expession levels of UNC5b gene in PCLTs were significantly correlated with capsular formation of HCC. Furthermore, RT-PCR results showed that the expression levels of UNC5b mRNA in activated HUAEC were significantly higher than those in normal HUAEC. Conclusions Down-regnlation of UNC5b gene expression is related to angiogenesis of HCC,which may be associated with the progression of HCC.