摘要
目的 :研究HBVX基因区关键区段的反义寡核苷酸 (asON)对人肝癌裸小鼠模型的抑瘤生长及体内抗HBV作用。方法 :PCR法分别合成了互补于HBVX基因的翻译起始区Xp、DR2、ENⅡ区的反义寡核苷酸及无关对照序列 ,进行硫代化修饰 ,以HBVDNA转染的HepG2 .2 .15细胞接种裸小鼠 ,2 4h内同部位一次性用药 10 0 μg ,观察并比较 3种反义硫代寡核苷酸的体内抑瘤作用。ELLSA法检测反义核酸作用裸小鼠血清中HBsAg和HBeAg含量的变化。结果 :3种药物作用裸小鼠组均表现为出瘤潜伏期延长 ,出瘤率明显低于未用药瘤细胞对照组 (P <0 .0 5 ) ,且瘤体生长缓慢。互补于Xp、DR2、ENⅡ区的反义寡核苷酸一次性给药方式对荷瘤鼠HBsAg和HBeAg的表达无明显抑制作用 ;无关序列不影响荷瘤鼠瘤体生长及HBV抗原表达。结论 :针对HBVX基因区关键部位的反义寡核苷酸可抑制荷瘤裸小鼠人肝癌的生长 。
Objective: To Study the growth inhibition effect of oligodeoxy- nucleotides on HBV X gene. Methods: Three antisense phosphorothioate oligodeoxy- nucleotides(asON) complementary to the initiator of Xp,DR2,ENⅡrespectively were synthesized through PCR method. Balb/c(nu/nu) mice were given asONs 100μg/mouse 24h after HepG2.2.15 cells 5 10 mouse were injected. The anti-HBV effect was assayed with ELISA. Results: In mice treated with as-Xp, as-ENII and as-DR2 treated a prolonged period of tumoregenesis as observed, but it was not found in the control group. There was no inhibition effect on the expression of HBsAg and HBeAg. Conclusion :These results demonstrated the anti-tumour activity of as-Xp, as-ENII and as-DR2 in vivo and the potential utility of short oligonucleotides as tumour cell inhibitors.
出处
《山东大学学报（医学版）》
CAS
2002年第3期193-194,198,共3页
Journal of Shandong University:Health Sciences
基金
国家自然科学基金课题 ( 30 0 70 341)
