反义端粒酶不同给予方式抑制裸鼠人肝癌模型生长的研究  

Antisense phosphorothioate oligodeoxynucleotides complementray to hTERT inhibits the growth of hepatoma cells by different ways in vivo

作　　者：刘素侠[1] 孙汶生[1] 韩丽辉[1] 马春红[1] 曹英林[1] 王晓燕[1] 

机构地区：[1]山东大学医学院免疫学研究所

出　　处：《山东大学学报（医学版）》2003年第1期16-18,共3页Journal of Shandong University:Health Sciences

基　　金：国家自然科学基金项目(30070341)

摘　　要：目的:研究人类端粒逆转录酶(hTERT)基因关键位点的反义寡核苷酸对人肝癌的抑制效应。方法:合成互补于hTERT关键区段的反义寡核苷酸(as-hTERT),以HBVDNA转染的HepG2.2.15细胞接种裸鼠制备人肝癌模型,通过连续用药、一次性用药、混合用药3种不同给予方式观察as-hTERT抑制瘤细胞生长作用。比较不同用药方法对裸鼠成瘤的影响,FCM分析as-hTERT诱导凋亡作用。结果:药物一次性与混合作用裸鼠表现为成瘤潜伏期延长,成瘤率明显低于瘤细胞未用药对照组(P<0.05),瘤体生长缓慢;追加用药后无瘤体生长。瘤内用药9dFCM测细胞凋亡峰为26.95%,G2～M期细胞为1.70%,对照瘤体的各细胞周期分布正常。结论:as-hTERT不同给予方式均可抑制荷瘤裸鼠人肝癌的生长,以追加用药效果最佳,具有潜在的临床应用价值。Objective:To Study the inhibition effect of antisense phosphorothioate oligodeoxynu-cleotides com ple mentary to the regulation region of hTERT(human telomerase reverse transcriptase)on the growth of hep atoma cells.Methods:BALB/c(nu/nu)mice were injected with HepG2.2.15cells to obtain nude mouse models of humanhepatocarcinoma .Three approaches were employed to study anti-tu mor ac tiv ity.In one growp,an imals were injected with HepG2.2.15cells,and2weeks later,tumors were estab lished,and then the ani mals were given as-hTERT and saline.In the second and third groups,animals infected with2.2.15cells as-hTERT100ug /mouse in one dose and in24hr,rehspectively.Re sults:Apop to sis was ob served in animals given100ug /mouse /day as-hTERT,but not in the saline-treated ani mals.A pro longed period of hepato carcinogenesis was observed in an imals of the second and third groups.Con clu sion:The re sults demon strated the anti-tumor activity of as-hTERT in vivo and the potential utili ty of as-hTERT as tu mor cell in hibitors.

关 键 词：端粒酶 反义寡核苷酸类 细胞凋亡 基因 肝癌 

分 类 号：R73－354[医药卫生—肿瘤] R735.7[医药卫生—临床医学]