Research progress on therapeutic strategies targeting the glutathione antioxidant system in cancer cells to reverse drug resistance
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摘要: 谷胱甘肽(glutathione,GSH )是维持生物体内氧化还原平衡状态最为重要的小分子活性寡肽,具有抗氧化和调节机体巯基平衡的作用,并通过参与谷胱甘肽化修饰调控众多信号转导分子及氧化还原敏感转录因子的活性。研究显示,在多种肿瘤中GSH 水平明显增高,通过消除ROS 、解毒药物或参与DNA 修复过程等机制促进肿瘤细胞耐药。GSH 系统代谢酶在耐药肿瘤细胞中亦呈高表达,调控肿瘤细胞对药物的治疗反应。耗竭GSH 或下调GSH 系统代谢酶可有效逆转肿瘤耐药,使耐药肿瘤细胞恢复化疗敏感性,表明GSH 抗氧化系统是促使肿瘤耐药的关键性因素之一。近年来,GSH 抗氧化系统作为潜在的抗肿瘤治疗和耐药逆转靶点正备受关注。本文就GSH 抗氧化系统参与肿瘤耐药的作用及GSH 抗氧化系统靶向药物作一综述。Abstract: Glutathione (GSH) is the most important small- molecule, active oligopeptide in the maintenance of redox balance. GSH contributes to antioxidant and thiol equilibrium, as well as modulates the activities of many signaling molecules and redox-sensi-tive transcription factors by S-glutathionylation. Several studies have shown that the GSH level increased in various tumors. Additional -ly, increased GSH significantly contributes to drug resistance by eliminating ROS, detoxifying drugs, or participating in DNA repair. GSH-related metabolic enzymes are overexpressed in resistant cells, thereby regulating cellular response to chemotherapy drugs. Deple-tion of GSH or downregulation of GSH-related metabolic enzymes may effectively reverse drug resistance and promote resistant cells to restore sensitivity. This potential indicates that the GSH antioxidant system plays an important role in drug resistance. The GSH anti -oxidant system, as a potential target for antitumor therapy and reversal of drug resistance, has recently become an attractive focus in cancer research. This paper presents a review of the role of the GSH antioxidant system in drug resistance and discusses the therapeutic strategies targeting the GSH antioxidant system.
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Keywords:
- glutathione /
- antioxidant /
- redox /
- cancer /
- resistance
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期刊类型引用(10)
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