PEG-PEI/Fe_3O_4纳米磁流体-TK对裸鼠移植性肝癌细胞靶向杀伤作用研究  

Effect of PEG-PEI/Fe_3O_4 Nano-magnetic fluid-TK on targeting therapy for implanted liver cancer in nude mice

作　　者：彭健[1] 刘桦[1] 刘路[1] 汤伟[1] 王荣兵[1] 陈伟[1] 曾杰[1] 邹芬[1] 周健[1] 

机构地区：[1]中南大学湘雅医院卫生部纳米生物技术重点实验室,湖南长沙410008

出　　处：《中国现代医学杂志》2008年第9期1162-1166,共5页China Journal of Modern Medicine

基　　金：国家自然科学基金(No:30672047);中国博士后科学基金(No:20060390884);湖南省博士后科学基金(No:2006FJ4240)

摘　　要：目的研究PEG-PEI/Fe3O4纳米磁流体-TK对人肝癌细胞系SMMC-7721裸鼠移植瘤模型的靶向性治疗作用。方法建立人原发性肝癌裸鼠皮下移植瘤模型,将荷瘤裸鼠随机分成肿瘤对照组、纯自杀基因组、PEG-PEI/Fe3O4纳米磁流体-TK组3组。对照组不作任何处理,实验组于瘤体内分别直接注射纯自杀基因、PEG-PEI/Fe3O4纳米磁流体-TK,同时于裸鼠腹腔内注射GCV,观察不同时段皮下肿瘤的生长情况并做病理学检查,免疫组化法检测肿瘤微血管密度(MVD)以及血管内皮细胞生长因子(VEGF)的表达量,原位末端标记(TUNEL)法检测细胞原位凋亡。同时,用RT-PCR检测肿瘤鼠心,肝,肾的自杀基因表达情况。结果裸鼠皮下成瘤率100%;研究PEG-PEI/Fe3O4纳米磁流体-TK组的肿瘤体积、血清AFP含量、肿瘤MVD和VEGF表达强度均明显低于对照组、纯自杀基因组(P<0.05),细胞凋亡指数都明显高于后两组(P<0.05),可见较多的凋亡细胞。RT-PCR测示肿瘤鼠心,肝,肾未见自杀基因表达,而肿瘤细胞则出现自杀基因表达。结论PEG-PEI/Fe3O4纳米磁流体-TK可显著抑制肿瘤的生长,并对肿瘤治疗具有靶向性,是一种较为理想的肝脏肿瘤靶向给药系统,有望成为治疗原发性肝癌的新型生物制剂之一。[Objective] To study the effects of PEG-PEI/Fe3O4 Nano-magnetic Fluid-TK targeting therapy for nude mice implanted liver cance with human SMMC-7721. [Methods] Human liver cancer cell line SMMC-7721 was implanted subcutaneously in nude mice to establish experimental animal model. Animals bearing liver cancer were randomly divided into three groups： control group, Thymidinekinase group; PEG-PEI/Fe3O4 Nano-magnetic fluid-TK. Different plasmids were directly injected into tumors and GCV was intra-peritoneally administrated simultaneously according to different groups. The growth of tumors was observed and the pathology was examined as well. The uhrastructural change of tumor cells was studied by using electron microscopy, the expressions of MVD and VEGF were respectively detected with immunohistochemistry and the cell apoptosis in situ was detected by TUNEL. Examines the tumor mouse suicide gene expression situation of heart the lung, kidney＇s with RT-PCR. [Results] The successful rate on establishing subcutaneous implanted liver cancer model in nude mice was 100%. The tumor volume, VEGF and MVD expressions of PEG-PEI/Fe3O4 Nano-magnetic fluid-TK group were lower than those in control group, Thymidinekinase group （P 〈0.05） and more apoptosis cells could be observed. The apoptosis index of PEG-PEI/Fe3O4 Nano-magnefic fluid-TK group was higher than that of the latter （P 〈0.05）. RT-PCR measured that shows the tumor mouse heart, the lung, the kidney has not seen the Thymidinekinase gene expression, but the tumour cell presents the Thyrnidinekinase gene expression. [Conclusion] PEG-PEI/Fe3O4 Nano-magnefie fluid-TK inhibits the growth of tumor remarkedly and becomes a promising new biological agent to treat human primary liver Cancer.

关 键 词：PEG—PEI/Fe3O4纳米磁流体-TK 肝癌 自杀基因 丙氧乌苷 靶向性治疗 

分 类 号：R318[医药卫生—生物医学工程]