乙酰肝素酶的外源性表达对大肠癌HT29细胞侵袭性的影响  

Effect of Exogenous Expression of Heparanase Gene on Invasive Ability of Colorectal Cancer Cell Line HT29

作　　者：刘玉[1] 丁彦青[2] 辛晓燕[1] 韩良辅 梁莉[2] 

机构地区：[1]第四军医大学西京医院妇产科,陕西西安710032 [2]南方医科大学肿瘤研究所,广东广州510515 [3]西安长安医院肿瘤部,陕西西安710016

出　　处：《癌症》2005年第12期1427-1430,共4页Chinese Journal of Cancer

摘　　要：背景与目的:乙酰肝素酶(heparanase,Hpa)基因表达与恶性肿瘤及肿瘤细胞的侵袭、转移和血管生成能力密切相关。本研究旨在通过增强肿瘤细胞中外源性Hpa基因的表达,探讨该基因对大肠癌细胞HT29转移侵袭能力的影响。方法:Hpa全长基因真核表达载体转染HT29细胞,MTT法检测转化细胞增殖能力,Boyden小室体外侵袭实验比较转染前后细胞侵袭能力的变化,通过转化细胞裸鼠异种接种成瘤和实体瘤回盲部原位种植转移模型建立,观察Hpa基因外源性表达对HT29细胞侵袭性的影响。结果:转染Hpa基因细胞HT29-Hpa较未转染细胞HT29和转染空载细胞HT29-KZ生长速度明显加快;Boyden小室体外侵袭实验显示,HT29-Hpa细胞穿膜数(45.5±0.5)较HT29细胞(29.3±0.1)和HT29-KZ细胞(30.1±0.2)增多,差异具有显著性(P<0.01)。转染细胞裸鼠皮下瘤生长速度明显加快,同期内HT29-Hpa细胞形成的皮下瘤(12mm×9mm×10mm)较HT29细胞皮下瘤(6mm×8mm×6mm)大,HT29-Hpa细胞皮下瘤回盲部原位种植致肝转移率(71.43%)较HT29细胞肝转移率(14.29%)增高,两者间有显著性差异(P<0.01)。结论:Hpa基因外源性的表达能促进肿瘤细胞的生长、侵袭和转移。BACKGROUND ＆ OBJECTIVE： Heparanase （Hpa） is an endoglycosidase that degrades heparin sulfate the main polysaccharide constituent of extracellular matrix （ECM） and basement. It can enhance the invasive and metastatic potential of malignant tumors and cell lines by destroying ECM and basement. This study was to explore the effects of heparanase gene on the invasive ability of colorectal cancer cell line HT29. METHODS： Heparanase gene was transfected into HT29 cells. Cell growth kinetics was assessed by MTT assay, and in vitro invasive ability was assessed with Boyden chamber. Xenograft and orthotopic implantation of histologically intact tumor in nude mice were constructed to observe the effect of exogenous expression of heparanase gene on invasive ability of HT29 cells. RESULTS： After transfection, the growth rate of heparanase-transfected HT29 （HT29-Hpa） cells was obviously higher than those of untransfected HT29 cells and empty vector-transfected HT29 （HT29-KZ） cells; the invasive cell number was significantly larger in HT29-Hpa cells than in untransfected HT29 cells and HT29-KZ cells （45.5±0.5 vs. 29.3±0.1 and 30.1±0.2, P〈0.01）. The entity neoplasm formed by HT29-Hpa cells （12mm×9mm×10mm） was bigger than that formed by untransfected HT29 cells （6mm×8mm×6mm）. The prevalence of liver metastasis caused by orthotopic implantation of xenograft was significantly higher in HT29-Hpa group than in control group （71.43% vs. 14.29%, P〈0.01）. CONCLUSION： Exogenous heparanase gene can facilitate the growth, invasion, and metastasis of HT29 cells.

关 键 词：大肠肿瘤 HT29细胞 乙酰肝素酶 基因转染 肿瘤转移 

分 类 号：R735.34[医药卫生—肿瘤]