原发性肝癌SDF-1/CXCR4轴与血管生成和病灶转移相关性研究  

Mechanism research of angiogenesis and metastasis of primary hepatic carcinoma regulated by SDF-1/CXCR axis

作　　者：李伟[1] 邢国辉[1] 董佃国[1] 

机构地区：[1]日照市中医医院胃肠肝胆学科部,山东日照276800

出　　处：《中华肿瘤防治杂志》2017年第9期606-610,共5页Chinese Journal of Cancer Prevention and Treatment

摘　　要：目的基质细胞衍生因子-1(stromal cell derived factor 1,SDF-1)是CXC趋化因子家族的一员,能够与其特异性受体CXCR4形成偶联分子对,参与肿瘤的恶性演进,是当前肿瘤治疗领域的重要分子靶标之一。原发性肝癌属于转移率较高的癌症之一,当前已有研究证实SDF-1/CXCR4轴与肝癌的血行转移和淋巴结转移密切相关,但其具体机制尚未明确。本研究分析原发性肝癌SDF-1/CXCR4轴与血管生成和病灶转移的关系,以完善其病理机制。方法选取日照市中医医院2014-01-26-2015-01-19治疗的原发性肝癌组织标本及其癌旁正常组织距(离病灶>2cm)31例。根据有无扩散或转移将31例原发性肝癌患者分为原位癌组(18例)和转移癌组(13例),癌旁组织为对照组(31例)。留取肝癌组织和癌旁正常组织,采用RT-PCR和蛋白质印迹法测定SDF-1与CXCR4的mRNA和蛋白表达水平;观察病理切片微血管密度(microvessel density,MVD),采用ELISA试剂盒测定血管内皮生长因子(vascular endothelial growth factor,VEGF)水平。同时体外培养人肝癌细胞株,行Transwell小室侵袭实验,测定梯度浓度(0、10、20、40和80μg/L)SDF-1干预下细胞侵袭数目。结果原位癌组、转移癌组和对照组SDF-1 mRNA表达水平分别为0.224±0.045、0.535±0.086和0.046±0.021,F=15.251,P<0.001;SDF-1蛋白表达水平分别为0.135±0.034、0.326±0.048和0.094±0.026,F=14.357,P<0.001;CXCR4 mRNA表达水平分别为0.505±0.086、0.974±0.103和0.334±0.072,F=18.236,P<0.001;CXCR4蛋白表达水平分别为0.432±0.044、0.706±0.085和0.045±0.033,F=21.425,P<0.001。原位癌、转移癌和对照组的MVD分别为11.5±3.2、24.6±5.2和7.35±1.1,F=13.256,P<0.001;VEGF分别为(148.6±13.2)、(356.2±21.5)和(46.8±7.3)ng/g,F=62.335,P<0.001。0、10、20、40和80μg/L的SDF-1干预对应的细胞侵袭数目分别为33.3±5.2、41.6±7.5、119.6±11.4、278.3±15.3和335.5±21.4,随着SDF-1干预浓度的增加,细胞侵袭数目逐渐增多,组间差异�OBJECTIVE Stromal cell derived factor 1（SDF-1）is a member of the CXC chemokines family,which forms coupling molecules with its specific receptor CXCR4.It takes important part in the malignant of tumor and is one of the important molecular targets for tumor therapy at present.Primary liver cancer has high transfer rate,the current studies have confirmed that the SDF-1/CXCR4 axis is closely related with the blood and lymph node metastasis of liver cancer,but the specific mechanism is not yet clear.Objective：This study aims to analyze the relationship between angiogenesis,metastasis and SDF-1/CXCR4 axis of primary hepatic carcinoma,so as to provide new idea for its clinical diagnosis and treatment.METHODS 31 hepatic carcinoma patients accepted in the TCM Hospital of Rizhao from January 26,2014 to January 19,2015 and treated by surgery were selected in this study,including 18 cases of carcinoma in situ and 13 cases of metastatic carcinoma.Both carcinoma tissues and normal adjacent mucosa were extracted,in which SDF-1and CXCR4 expression levels were detected with RT-PCR assay and WB assay.The microvessel density（MVD）was observed through immunohistochemical experiment,and the VEGF level was detected through ELISA kits.The number of HCC invading cells were detected in a vitro invasion assay.RESULTS The SDF-1mRNA expression levels of the preinvasive carcinoma,metastatic carcinoma and the controls were 0.224±0.045,0.535±0.086,0.046±0.021,F=15.251,P〈0.001;the SDF-1protein expression levels were 0.135±0.034,0.326±0.048,0.094±0.026,F=14.357,P〈0.001;the CXCR4SDF-1mRNA expression levels were 0.505±0.086,0.974±0.103,0.334±0.072,F=18.236,P〈0.001;the CXCR4 protein expression levels were 0.432±0.044,0.706±0.085,0.045±0.033,F=21.425,P〈0.001.The MVD of he preinvasive carcinoma,metastatic carcinoma and the controls were 11.5±3.2,24.6±5.2,7.35±1.1,F=13.256,P〈0.001;the VEGF were（148.6±13.2）,（356.2±21.5）,（46.8±7.3）ng/g,F=62.335,P〈0.001.With the increase of SDF-1concentration,the number

关 键 词：基质细胞衍生因子-1 原发性肝癌 血管生成 病灶转移 

分 类 号：R735.7[医药卫生—肿瘤]