受体介导的C-myc反义核酸抑制肝癌移植瘤生长  

The Inhibition of Receptor-Mediated C-myc Antisense Oligodeoxynucleotides on the Growth of Transplanted Hepatocarcinoma in Mice

作　　者：蒋建伟[1] 张洹 

机构地区：[1]暨南大学医学院血液病研究所,广州市510630 [2]不详

出　　处：《中国肿瘤临床》2006年第22期1307-1309,1311,共4页Chinese Journal of Clinical Oncology

基　　金：广东省自然科学基金重点项目(编号:021195);广东省自然科学基金资助(编号:04010487)

摘　　要：目的:探讨半乳糖(galactose,Gal)受体介导的C-myc反义核酸对肝癌移植瘤生长的抑制作用。方法:将C-myc反义寡核苷酸(antisenseoligodeoxynucleotide,ASODN)与半乳糖-聚乙烯亚胺(polyethyleneimine,PEI)转染载体作用形成Gal-PEI-ASODN复合物,采用荧光显微镜检测荧光标记反义核酸进入人肝癌Bel-7402细胞的形态,克隆形成实验观察反义核酸对细胞克隆形成的影响,用肝癌移植瘤小鼠模型观察反义核酸对肝癌移植瘤的生长抑制作用,免疫组化技术检测肝癌组织C-myc蛋白的表达。结果:Gal-PEI-ASODN复合物能被肝癌Bel-7402细胞有效摄取,荧光标记的反义核酸分布在细胞的表面、胞浆、胞核部位;Gal-PEI-ASODN复合物对肝癌细胞克隆形成有明显抑制作用,与细胞对照组相比,差异显著(P<0.01)。Gal-PEI-ASODN复合物能显著抑制小鼠肝癌移植瘤的生长,肿瘤抑制率为40.25%,与细胞对照组相比,差异显著(P<0.01);有可能抑制瘤细胞内C-myc蛋白的表达。结论:半乳糖受体介导的C-mycASODN能有效抑制Bel-7402细胞的增殖,抑制小鼠肝癌移植瘤的生长,阻断C-myc蛋白的表达。Objective： To investigate the inhibition of c-myc antisense oligodeoxynucleotides mediated by receptor on the growth of mice transplanted hepatocarcinoma. Methods： C-myc ASODN was mixed with galactose （Gal）- polyethyleneimine （PEI） reagent forming Gal-PEI-ASODN complex. The morphology of fluorescence-labeled Gal-PEI-ASODN entering Bel-7402 cells was observed under fluorescence microscope. Cell clones were counted by inverted microscope and the clone forming rates were calculated. Mice transplanted hepatocarcinoma model of Hep A cells was setting up, tumor inhibition rates were measured and C-myc protein expression level was examined by immunohistochemical method. Results： Gal-PEI-ASODN complexes could be imbibed by Bel-7402 cells effectively, fluorescence-labeled ASODN particles distributed on cell membrane surface, in cytoplasm or in nucleus. Gal- PEI-ASODN complexes inhibited cell clone forming significantly compared with the cell control group （P〈0.01）. Gal-PEI-ASODN complexes inhibited the growth of mice hepatocarcinoma with the tumor inhibition rate 40.25% （P〈0.05） and blocked the expression of C-myc protein in hepatocarcinoma cells. Conclusions： C-myc ASODN mediated by galactose receptor can effectively inhibit the proliferation of Bel-7402 cells and the growth of transplanted hepatocellular carcinoma and the expression of C-myc protein in hepatocarcinoma cells in mice.

关 键 词：C-MYC 反义寡核苷酸 肝癌 半乳糖 

分 类 号：R735.7[医药卫生—肿瘤]