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.
出处
《山东大学学报（医学版）》
CAS
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)
