金诺芬与其他药物联用增强对实体瘤杀伤作用的研究进展

Research Progress in Enhancing the Killing Effect of Auranofin in Combination with Other Drugs on Solid Tumors

关键词:  金诺芬  硫氧还蛋白  肿瘤  老药新用  药物联用

Key words:  auranofin  thioredoxin  cancer  drug repurposing  drug combination

摘要:

硫氧还蛋白还原酶（thioredoxin reductase，TrxR）抑制剂金诺芬（auranofin）是一种含+1价金的化合物，过去被美国FDA批准用于治疗风湿性关节炎。近年来发现，金诺芬在部分实体瘤中具有抗肿瘤活性。其主要通过抑制硫氧还蛋白还原酶来诱导肿瘤细胞凋亡，同时也可抑制肿瘤细胞的增殖以及迁移侵袭，从而发挥抗肿瘤作用。金诺芬现阶段已经批准用于卵巢癌和肺癌的临床试验。虽然金诺芬在许多研究中表现出良好的抗肿瘤作用，但金诺芬的单药治疗始终无法达到理想的效果，也正因如此，越来越多的研究团队将研究重点放在金诺芬的联合用药上。在肿瘤研究中，金诺芬被证实与多种药物之间有联合效应。本文就金诺芬与其他药物联合运用以增强其抗肿瘤活性的研究进展进行了综述，为金诺芬在肿瘤治疗中的联合用药提供一些思路及策略。

Abstract:

Auranofin, a gold(I) compound, is a thioredoxin reductase inhibitor previously approved by the U.S. FDA for the treatment of rheumatoid arthritis. Auranofin has been found to have anti-tumor activity in some solid tumors. Auranofin exerts anti-tumor activity of inhibiting proliferation, migration and invasion of tumor cells via inducing apoptosis by inhibiting thioredoxin reductase. Auranofin is currently approved in clinical trials for the treatment of ovarian and lung cancers. Although auranofin has shown good anti-tumor effect in many studies, the effect of single auranofin treatment is still not desirable. This leads to further research of auranofin combination therapy. Recently progress has shown that auranofin in combination with several drugs achieve has desirable outcomes. In this review, the studies of auranofin combination therapy was summarized, and some ideas and strategies was provided for the combination of auranofin and other drugs in cancer treatment.