异靛甲体外抑制DNA和RNA生物合成的抗癌作用机理  

Mechanism of inhibitory action of meisoindigo on DNA and RNA biosyntheses in vitro

作　　者：刘晓梅[1] 王龙贵[1] 籍秀娟[1] 

机构地区：[1]中国医学科学院药物研究所,北京100050

出　　处：《中国药理学与毒理学杂志》1991年第3期204-208,共5页Chinese Journal of Pharmacology and Toxicology

基　　金：国家自然科学基金 No 39070938

摘　　要：以同位素参入法及光谱法观察异靛甲对核酸合成的抑制作用和药物与DNA相互作用。结果表明,异靛甲对DNA,RNA合成有较强的抑制作用,其IC_(50)分别为9和15μmol/L,药物作用非常迅速。30μmol/L异靛甲作用15μmin后DNA,RNA合成被抑制95％以上。实验还表明,异靛甲不能损伤DNA模板,也不抑制DNA拓扑异构酶及DNA多聚酶Ⅰ,但能明显抑制T7 RNA多聚酶,在’100μmol/L浓度下对mRNA的合成抑制达70％以上。Meisoindigo, an indirubin derivative, is a new type of cancer chemotherapeutic agent. It exhibited higher activity against rodent tumors than indirubin itself. In this paper, the effects of meisoindigo on DNA and RNA biosyntheses in Walker 256 (W256) cells and the mechanism of the action were reported. Experiments revealed that meisoindigo had a remarkable inhibitory effect on the biosythesis of DNA and RNA in W256 cells. The 1C50 was 9 and 15 μmol / L respectively. Dynamic studies showed that the inhibitory effect of meisoindigo on both DNA andRNA was very fast, more than 95% of DNA and RNA syntheses were terminated after the W256 cells were treated with the drug (30μmol / L) for 15 min and there was no significant difference between DNA and RNA syntheses in the kinetic procedures when the W256 cells were exposed to the agent. In order to recognize the mechanism of the inhibition, the reaction of meisoindigo between DNA templet, DNA polymerase, DNA polymerase I and T7 RNA polymerase was studied. The experiments showed that the agent did not damage DNA templet by intercalation or covalent binding and had no direct significant inhibition on was added to the reaction system. DNA topoisomerage and DNA polymerase I. However, the drug had a remarkable inhibitory effect on T7 RNA polymerase and almost 70% of T7 mRNA was inhibited when 100μmol / L meisoindigo

关 键 词：异靛甲 脱氧核糖核酸 核糖核酸 

分 类 号：R968[医药卫生—药理学]