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为了研究血管内皮细胞生长因子(VEGF)及其受体(flk-1)系统在人肝癌血管形成、生长和转移过程中的作用,探讨预测和防治肝癌转移和复发的新途径,我们采用了仅表达flk-1蛋白的膜外和跨膜部分的突变型基因片段,与逆转录病毒载体pLXSN构建重组体,经过病毒包装,体内原位转染荷人肝癌转移瘤株LCI D-20裸鼠.结果显示,在被突变型flk-1转染的皮下肿瘤生长缓慢,21天时的平均体积为102.2mm~3,对照组为1374.5mm~3,两组相比P<0.01;肿瘤组织中新生血管极少,团状排列的肿瘤细胞被大量的纤维组织包裹,对照组新生血管丰富.细胞增殖活跃;肝内接种肿瘤转染后肺转移灶亦明显少于对照组,P<0.05.结果提示,VEGF/flk-1系统在肝癌血管形成、生长和转移过程中发挥重要作用,是预测和防治肝癌转移和复发较为理想的靶分子.
To investigate the role of vascular endothelial growth factor (VEGF) and its receptor (flk-1) system in angiogenesis, growth and metastasis of human hepatocellular carcinoma and to explore new ways to predict and prevent the metastasis and recurrence of hepatocellular carcinoma, we used only The mutant gene fragment expressing the extracellular and transmembrane portions of flk-1 protein was constructed with recombinant retroviral vector pLXSN. After viral packaging, the transfected human hepatocellular carcinoma cell line LCI D-20 nude mice were transfected in situ. The results showed that the subcutaneous tumors transfected with the mutant flk-1 grew slowly, with an average volume of 102.2mm ~ 3 at 21 days and 1374.5mm ~ 3 in the control group, P <0.01 compared with the two groups; neovascularization Very few tumor cells arranged in clusters were surrounded by a large number of fibrous tissue, the control group of new blood vessels rich in cell proliferation active; liver metastases after transfection of intrahepatic inoculation was also significantly less than the control group, P <0.05.Results, The VEGF / flk-1 system plays an important role in angiogenesis, growth and metastasis of hepatocellular carcinoma and is an ideal target for predicting and preventing the metastasis and recurrence of hepatocellular carcinoma.