抗癌药物对DNA拓扑异构酶活性的影响

Unknotting Activity of DNA Topoisomerase Ⅱ in Actively Proliferating Cells and Inhibition of the Activity by Antitumoral Drugs

本文比较了正常组织与肿瘤组织中DNA拓扑异构酶Ⅱ的活力,证实异常增殖的肿瘤组织或细胞的酶活力较正常组织高。同对,我们选用了几类有代表性的抗癌药物或中草药成分,观察了它们对拓扑异构酶Ⅱ的影响。结果表明一些抗癌药物在低浓度时对Ⅱ型酶的解结反应等有明显的抑制作用。因此,肿瘤组织中解结活性异常增高说明Ⅱ型酶可能是抗癌药物的一种靶蛋白;对解结活性的抑制有可能为寻找新的抗癌药物提供一条途径。

It has been suggested that DNA topoisomerases might be either highly active or produced in large amounts in tumor cells and could be important targets for several drugs used in cancer therapy .Here, we compared the activity of topoiso-merase Ⅱ prepared from many types of tissues and cultured cells.we found that the unknotting activity of the enzyme in tumor cells was higher than that in normal liver cells.This suggests that we could expect to assay antitumoral drugs by monitoring the inhibition of the unknotting activity. Therefore we selected antitumoral drugs which action on topoisomerase Ⅱ was either known or unknown, including some Chinese traditional medicine, and observed their effects on the unknotling activity.The results showed that inhibition of the unknotting activity required very low concentrations of some drugs,but much higher concentrations were required for some othsr drugs tested. We also found that some antitumoral drugs had no effect on the enzyme. It is interesting that carrageenan, an antiviral drug, strongly blocked the unknotting activity although its antitumoral activity has not been reported.