缺氧诱导因子_

Angiostatin基因治疗人肝癌裸鼠移植瘤的实验研究

http://www.100md.com 《中国普通现代外科进展》 2005年第5期

缺氧诱导因子,,基因，Angiostatin·血管内皮细胞生长因子·缺氧诱导因子·基因疗法·肝肿瘤·小鼠，近交BALB,C,1材料和方法,2结果,3讨论,参考文献

     【摘要】目的：研究Angiostatin基因治疗对人肝癌裸鼠皮下移植瘤的抑制作用及其相关机理。方法：使用人原发性肝癌细胞株SMMC7721建立人肝癌裸鼠皮下移植瘤动物模型，质粒用脂质体DOTAP介导转染细胞。将荷瘤裸鼠随机分为两组，分别注射质粒PcDNA3、Angiostatin/PcDNA3，观察两组动物的肿瘤生长曲线，检测肿瘤的Angiostatin、VEGF、HIF1α表达和微血管密度(MVD)，利用TUNEL染色法行原位细胞凋亡分析。结果：Angiostatin基因治疗在早期具有抑制肿瘤生长的作用，大约1周后肿瘤以更快的速度生长并迅速赶上空质粒对照组肿瘤；Angiostatin基因治疗组的肿瘤组织中有Angiostatin的局部高表达，MVD(24.8±2.8)低于空质粒对照组(30.2±4.1)(P0.05)。肿瘤组织中HIF1α蛋白局部高表达，VEGF表达高于空质粒对照组，细胞凋亡指数(2.87±0.48)高于空质粒对照组(1.55±0.43)(P0.01)。结论：Angiostatin基因治疗对人肝癌裸鼠皮下移植瘤的生长具有一定的抑制作用，肿瘤对Angiostatin基因治疗可以产生耐受性。

    【关键词】基因，Angiostatin·血管内皮细胞生长因子·缺氧诱导因子·基因疗法·肝肿瘤·小鼠，近交BALB C

    Experimental study on the effect of angiostatin on implanted human primary hepatic carcinoma in nude mouse

    DONG Dianning1,SUN Ping,ZHI Xuting,SUN Xueying,SHOU Nanhai

    Department of General Surgery,Shandong Provincial Hospital(Jinan 250021,China)

    Department of Obstetrics and Gynecology,3Department of General Surgery，Qilu Hos

    pital of Shandong University(Jinan 250012,China)

    【ABSTRACT】Objective:To observe the effects of angiostatin gene on implanted human primary hepatic carcinoma in nude mouse.Methods:Tumors were established by injection of 3×106 tumor cells named SMMC7721 into the back of nude mice.The mice were classified randomly into two groups,injected respectively with vacant plasmid PcDNA3,angiostatin plasmid.Half of the nude mice were used to observe the tumor growth curve,the other half to obtain the tumor samples.The tumor samples were prepared in the 4th day after gene transfer to be used in the examinations ofthe expression of angiostatin,HIF1α and VEGF with immunohistochemistry and Western blot analysis,of MVD in the tumor with immunohistochemistry,and of cell apoptosis with TUNEL staining.Results:Tumor grew rapidly in the control group,whereas,in the angiostatin group,tumors were suppressed for one week after gene transfer,then they grew even faster and caught up with control group tumors.Immunohistochemistry analysis and Western blot analysis of tumor tissue revealed angiostatin gene therapy resulted in overexpression of angiostatin in situ.In addition,the expression of VEGF in the angiostatin group is a little higher than that in the control group.AI in the angiostatin group is higher than that in the control group(P0.01),concurrently MVD is lower(P0.05).Conclusion:The angiostatin gene therapy can inhibit the tumor growth in some degree,but the tumor can obtain resistance to angiostatin gene therapy by hypoxia inducible factor. ......

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