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硫氧还蛋白系统概述及急性白血病的靶向治疗。

Overview of thioredoxin system and targeted therapies for acute leukemia.

机构信息

Department of Hematology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei 430071, China.

Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China.

出版信息

Mitochondrion. 2019 Jul;47:38-46. doi: 10.1016/j.mito.2019.04.010. Epub 2019 Apr 25.

Abstract

The thioredoxin (Trx) system is a major antioxidant system for keeping the intracellular redox state in almost all forms of life, including Trx, Trx reductase (TrxR) and NADPH. It regulates many signaling pathways related to antioxidative action, growth promotion, anti-apoptosis, cell migration, inflammatory modulation, immune function, etc. The oxidative stress has been proved to promote cancer occurrence and the readjustment of Trx system. Considerable results have demonstrated overexpression of Trx in cancer cells, moreover, the overexpression of Trx is closely related to high risk of cancer recurrence and drug resistance. This review focuses on the relationship between Trx system and acute leukemia (AL). The crux of the development of any useful therapy is a knowledge of disease etiology and progression. The potential of thioredoxin system inhibitors as therapeutic agents for acute leukemia is highlighted. Furthermore, targeting Trx as an anti-leukemic strategy is clinically beneficial to AL patients.

摘要

硫氧还蛋白(Trx)系统是几乎所有生命形式中维持细胞内氧化还原状态的主要抗氧化系统,包括 Trx、Trx 还原酶(TrxR)和 NADPH。它调节许多与抗氧化作用、促进生长、抗细胞凋亡、细胞迁移、炎症调节、免疫功能等相关的信号通路。氧化应激已被证明可促进癌症的发生和 Trx 系统的重新调整。大量研究结果表明,Trx 在癌细胞中过度表达,此外,Trx 的过度表达与癌症复发和耐药的高风险密切相关。本综述重点关注 Trx 系统与急性白血病(AL)的关系。任何有用疗法的发展关键在于对疾病病因和进展的了解。硫氧还蛋白系统抑制剂作为急性白血病治疗药物的潜力得到了强调。此外,将 Trx 作为抗白血病策略靶向治疗对 AL 患者具有临床益处。

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