靶向硫氧还蛋白系统治疗癌症。

Targeting the Thioredoxin System for Cancer Therapy.

机构信息

State Key Laboratory of Applied Organic Chemistry, and College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, China; School of Pharmacy, Lanzhou University, Lanzhou, 730000, China.

State Key Laboratory of Applied Organic Chemistry, and College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, China.

出版信息

Trends Pharmacol Sci. 2017 Sep;38(9):794-808. doi: 10.1016/j.tips.2017.06.001. Epub 2017 Jun 22.

DOI:10.1016/j.tips.2017.06.001

PMID:28648527

Abstract

Thioredoxin (Trx) and thioredoxin reductase (TrxR) are essential components of the Trx system which plays pivotal roles in regulating multiple cellular redox signaling pathways. In recent years TrxR/Trx have been increasingly recognized as an important modulator of tumor development, and hence targeting TrxR/Trx is a promising strategy for cancer treatment. In this review we first discuss the structural details of TrxR, the functions of the Trx system, and the rational of targeting TrxR/Trx for cancer treatment. We also highlight small-molecule TrxR/Trx inhibitors that have potential anticancer activity and review their mechanisms of action. Finally, we examine the challenges of developing TrxR/Trx inhibitors as anticancer agents and perspectives for selectively targeting TrxR/Trx.

摘要

硫氧还蛋白（Trx）和硫氧还蛋白还原酶（TrxR）是 Trx 系统的必需组成部分，该系统在调节多种细胞氧化还原信号通路中发挥关键作用。近年来，TrxR/Trx 被越来越多地认为是肿瘤发展的重要调节剂，因此靶向 TrxR/Trx 是一种有前途的癌症治疗策略。在这篇综述中，我们首先讨论了 TrxR 的结构细节、Trx 系统的功能以及针对 TrxR/Trx 进行癌症治疗的合理性。我们还强调了具有潜在抗癌活性的小分子 TrxR/Trx 抑制剂，并回顾了它们的作用机制。最后，我们研究了开发 TrxR/Trx 抑制剂作为抗癌药物的挑战，并探讨了选择性靶向 TrxR/Trx 的前景。