【摘要】 目的 :研究反义寡核苷酸 (antisenseoligonucleotides)对人体引起急性早幼粒细胞白血病的HL 6 0细胞增殖和蛋白质表达的抑制作用。方法 :设计和合成了不同序列、长度和核苷酸磷酸根上有无修饰的多种脱氧寡核苷酸片段 ,进行了对HL 6 0细胞的生长抑制和蛋白表达的抑制试验 ,也测定了它们对人体正常淋巴细胞的毒性。结果 :发现互补于C mycmRNA的 2个区域的反义寡核苷酸序列 (5′ 4 4 6 1和 5′ 556 576 )有较好的抑制效率 ,在一定时间内 ,HL 6 0细胞增殖抑制分别达到 59.5%和6 2 .7% ,并且它们对人体正常淋巴细胞无毒性作用。结论 :我们新设计的互补于 5′ 4 4 6 1序列片段对HL 6 0细胞增殖有抑制作用 ,有望发展成抑制HL 6 0细胞增殖的核酸药物。更多还原

【Abstract】 AIM: To study on antisense oligoncleotides as inhibitor of human acute promyelocytic leukemia (HL 60) proliferation and C myc protein expression. METHODS: Oligonucleotides with different lengths (18 21 mer) complementary to the definite regions of C myc mRNA, modified groups (with S replaced O in internucleotide phosphate linkage) and unmodified ones (with natural internucleotide phosphate linkage) were designed and synthesized. These olignucleotides were tested for their activity on HL 60 cell and also for their toxicity on normal lymphatic cells of human. RESULTS: It was found that two of the oligonucleotides complementary to 5′ 44 61 and 5′ 556 576 the regions of C myc mRNA exhibited great inhibitory effects (59.5 % and 62.7 %) on growth of HL 60 cells for a definite time. And no toxicity of the two antisense oligonucleotides was found on normal lymphatic cells of human. CONCLUSION: The sequence of antisense oligonucleotides complementary to 5′ 44 61 of C myc mRNA was designed newly by us may be turned into inhibitory medicine of HL 60 cells.更多还原