阿霉素的氧化还原生物学：氧化还原循环、拓扑异构酶抑制与氧化应激
Doxorubicin Redox Biology: Redox Cycling, Topoisomerase Inhibition, and Oxidative Stress.
作者信息
Zhu Hong, Sarkar Soumyadeep, Scott Laura, Danelisen Igor, Trush Michael A, Jia Zhenquan, Li Y Robert
机构信息
School of Osteopathic Medicine, Campbell University, Buies Creek, NC 27506, USA.
College of Pharmacy and Health Sciences, Campbell University, Buies Creek, NC 27506, USA.
出版信息
React Oxyg Species (Apex). 2016;1(3):189-198. doi: 10.20455/ros.2016.835.
Abstract
Doxorubicin (also called Adriamycin) is effective in treating a wide range of human cancers and currently considered as one of the most important drugs in cancer chemotherapeutics. The clinical use of doxorubicin is, however, associated with dosage-dependent cardiotoxicity and development of heart failure, which diminish the therapeutic index of this widely used anticancer drug. This article first surveys key research findings on doxorubicin redox biology that may impact its cardiotoxicity as well as anticancer activity. It then discusses emerging concepts, especially the topoisomerase IIb-p53-mitochondrion axis that may lead to the development of mechanistically based novel strategies to protect against cardiotoxicity and enhance the effectiveness of doxorubicin therapy.
摘要
阿霉素（也称为多柔比星）在治疗多种人类癌症方面有效，目前被认为是癌症化疗中最重要的药物之一。然而，阿霉素的临床应用与剂量依赖性心脏毒性和心力衰竭的发生有关，这降低了这种广泛使用的抗癌药物的治疗指数。本文首先综述了关于阿霉素氧化还原生物学的关键研究发现，这些发现可能会影响其心脏毒性以及抗癌活性。然后讨论了新出现的概念，特别是拓扑异构酶IIb-p53-线粒体轴，这可能会导致开发基于机制的新策略，以预防心脏毒性并提高阿霉素治疗的有效性。
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