Na^+-H^+交换体1反义基因磁性纳米微粒体内靶向治疗胃癌的实验研究  

Study on the targeting therapeutic effects of Na^+-H^+ exchanger 1 antisense gene magnetic nanoparticles on gastric cancer

作　　者：刘海峰[1] 陈刚[2] 滕小春[2] 汪兴伟[2] 张爽[1] 

机构地区：[1]武警总医院消化科,北京100039 [2]第三军医大学西南医院消化科

出　　处：《胃肠病学和肝病学杂志》2009年第1期52-56,共5页Chinese Journal of Gastroenterology and Hepatology

基　　金：武警部队科研基金项目(No.WZ200511和No.WZ200415)资助

摘　　要：目的探讨Na+-H+交换体1(NHE1)反义基因磁性纳米微粒体内靶向治疗胃癌的可行性。方法构建NHE1反义基因真核表达载体和NHE1反义基因磁性纳米微粒,以氧化铁磁性纳米颗粒为基因转染载体,将NHE1反义基因导入SGC-7901胃癌细胞中,获得稳定表达NHE1反义基因的7901-AS细胞。研究转染细胞形态学变化及体外生长情况。建立裸鼠胃癌移植瘤模型后,进行体内靶向定位实验,观察抑瘤率。结果7901-AS细胞在光镜、电镜下的肿瘤细胞形态恶性程度降低,出现显著生长抑制现象,细胞增殖指数降低,凋亡指数明显增高(P<0.01)。实验组肿瘤组织铁含量为(79.38±8.64)μg/g,显著高于对照组[(38.13±9.37)μg/g,P<0.01]。NHE1反义基因磁性纳米微粒+磁场组抑瘤率为32.83%,高于NHE1反义基因磁性纳米微粒组1.51%和磁场组0.75%。NHE1反义基因磁性纳米微粒+磁场组裸鼠瘤体质量为(1.78±0.30)g,显著低于生理盐水对照组[(2.65±0.42)g,P<0.01]、NHE1反义基因磁性纳米微粒组[(2.61±0.49)g,P<0.05]和磁场组[(2.63±0.51)g,P<0.05]。结论利用多聚赖氨酸修饰的氧化铁纳米颗粒为基因载体,完成了NHE1反义基因对SGC-7901胃癌细胞株的转染,NHE1反义基因对SGC-7901胃癌细胞株的恶性行为有明显的抑制作用。在磁场作用下成功实现了NHE1反义基因在裸鼠体内针对肿瘤的磁靶向定位,并产生了显著的抑制作用。初步证明了磁性纳米材料体内靶向基因治疗胃癌的可行性,为肿瘤治疗提出了一个新的探索方向。Objective To study the effects of Na^＋-H^＋ exchanger 1 （NHE1） antisense gene magnetic nanoparticles on the biological behaviors of gastric carcinoma cell line SGC-7901 and the potentiel role in the targetic gene therapy for cancers. Methods The dextran coated iron oxide nanoparticles （DCIONP） was synthesized with deposition. NHEl antisense gene eukaryotic expression plasmid was transfected into SGC-7901 gastric carcinoma cells by DCIONP. Changes of cell proliferative capacity, apoptosis, cell cycle, clone formation in two-layer soft agar and tumorigenicity in nude mice were examined. After the model of transplanted gastric cancer established in nude mice, magnetic field was applied to investigate the target distribution of NHE1 antisense gene magnetic nanoparticles in transplanted gastric cancer in nude mice. Results Antisense eukaryotic expressing vectors were successfully constructed and transfected into SGC-7901. The malignant phenotypes of SGC-7901 cells transfected with antisense NHE1 partially reversed. Compared with SGC- 7901 and 7901-Zeo cells, 7901-AS cells mainly showed cell proliferation inhibition, increasing cell apoptotic rate, recovery of contact inhibition and density contact, the tumorigenicity in nude mice and cloning efficiency in two-layer soft agar were obviously inhibited. The Fe concentration in tumor tissue （79.38± 8.64） μg/g was remarkably higher than that in control group [ （38.13 ±9.37） μg/g, P 〈 0.01 ]. The tumor weight of NHE1 antisense gene magnetic nanoparticles added magnetic field group （1.78 ± 0.30）g was less than those of NS and NHE1 antisense gene magnetic nanoparticles groups [ （2.65 ± 0.42） g, （2.61 ±0.49） g ] , there was statistic difference （ P 〈 0.01 and P 〈 0.05 ）. Conclusion Our study demonstrates that NHE1 antisense gene could significantly restrain the malignant behavior of human gastric carcinoma cells, significantly suppress cell growth and induce cell apoptgsis, partially reverse malignant phenotypes of SGC-7901. Guid

关 键 词：Na^+-H^+交换体1 磁性纳米微粒 反义基因 靶向治疗 胃癌 

分 类 号：R735.2[医药卫生—肿瘤]