以硫氧还蛋白和硫氧还蛋白还原酶为靶点的抗癌药物

Anticancer agents targeting thioredoxin and thioredoxin reductase

硫氧还蛋白系统由硫氧还蛋白(Trx)、硫氧还蛋白还原酶(TrxR)及NADPH组成。Trx和TrxR在多种肿瘤组织中过表达。以Trx为靶点的化合物通过与其半胱氨酸残基相结合或增强其内源性抑制因子的表达水平,抑制肿瘤细胞生长。TrxR是体内唯一能还原Trx的酶。许多化合物能够靶向TrxR活性位点处的硒代半胱氨酸残基,导致氧化态Trx堆积,亦可增加其NADPH氧化酶活性,导致ROS(reactive exygen species)的产生。本文将对Trx/TrxR与癌症的关系及以Trx/TrxR为靶点的抗癌药物的研究进展做一综述。

The thioredoxin system contains thioredoxin （Trx）, thioredoxin reductase （TrxR） and NADPH. Trx and TrxR are overexpressed in various cancer tissues. The compounds suppress tumor cell growth by binding to the cysteine residue of Trx, or upregulating the activity of an endogenous inhibitor of Trx. TrxR is the only enzyme in the cell which reduces oxidized Trx. A number of compounds, which target the selenocysteine-containing active site of TrxR, can lead to an accumulation of oxidized Trx and increase the activity ofNADPH oxidase. This paper will review the advances in TrrdTrxR and cancer and the anticancer agents that target Trx/TrxR.