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[摘要]
目的: 研究嵌合寡核酸对端粒酶活性的抑制作用。 方法: 合成各种寡核苷酸(ODNs),利用HL-60细胞溶解液实施体外实验,U 87细胞系观察这些寡核苷酸在细胞水平的作用。 结果: 硫代磷酸酯寡核甘酸(PS ODNs)和RNA模板反义ODNs都可以抑制端粒酶的活性,且可产生累积效应。PS-ODNs的3′端延长一段与端粒酶RNA模板区域互补的各种修饰的ODNs则可以更进一步地提高它们的抑制效率。 结论: 研究设计的嵌合反义寡核苷酸(cODNs)作为目前较有效的端粒酶活性抑制剂,可成为肿瘤治疗中较有前途的药物之一。
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[Abstract]
Objective: To investigate the inhibitory effect of telomerase activity by chimeric oligonucleotide.Methods: Here various oligonucleotides were designed and synthesized. Inactivity of the telomerase activity inhibitors was observed with HL-60 cell-lysates in vitro and with U-87 clell in vivo. Results: Both phosphorothioate-modified oligonuclotides (PS-ODNs) and oligonucleotides complementary with telomerase RNA template inhibited telomerase activity. And application of the tow ODNs together increased the inhibition activity in upfold. the various modification extensional oligonucleotides complementary with telomerase RNA template at 3′-end of the PS-ODNs enabled the chimeric oligonucleotides to increase their inhibition efficiency. Conclusion: These cODNs emerged as powerful inhibitors of human telomerase detected so for and might be promising candidates to investigate the effect of permanent of inhibition of telomerse on tumor growth.
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