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沉默cdk7基因对hepg2细胞株的抗增殖作用

, PP. 58-61

Keywords: 细胞周期蛋白依赖激酶7,肝细胞癌,反义寡脱氧核苷酸

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Abstract:

目的筛选对体外培养hepg2细胞抗增殖作用最强的反义寡脱氧核苷酸(anti-senseoligodeoxynucleotides,asodn)序列,探讨经二次优化后该asodn片段的抗增殖作用。方法根据rnastructure3.71计算机软件模拟人cdk7mrna获得的二级结构确定待选asodn,经oligowalk程序分析这些片段与mrna互补时的热力学参数变化,以此优选待筛asodn,以体外培养人肝癌hepg2细胞为筛选体系获得抗增殖作用最强的asodn,对该片段分别依次向互补区上、下游错位1~5个碱基获得10条asodn,经结构优化后进行二次筛选。结果初筛结果显示互补于人cdk7mrna第284~303片段的部分硫代修饰asodn抗增殖作用最强,为(40.4±12.6)%;二次筛选显示互补于第287~306片段的全磷酸硫代修饰asodn抗增殖作用最强,抑制率为(68.3±2.6)%,半数抑制浓度为(51.9±8.6)nmol/l。结论筛选得到的asodn片段可显著抑制体外培养hepg2细胞的增殖,有可能作为先导化合物开发特异性cdk7抑制剂。

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