铜离子转运蛋白家族与肺癌顺铂耐药的研究进展

Research progress on copper ion transport protein family and cisplatin drug resistance in lung cancer

铂类药作为化疗一种关键药之一，被广泛用于治疗各种恶性肿瘤，如卵巢、膀胱、头颈部肿瘤及肺癌。但铂类耐药的发生限制了化疗反应，影响了患者的预后。目前在铂类耐药的机制方面已经有一些重要的发展，其中之一是肿瘤铂类耐药与细胞内浓度的蓄积之间的相关性，摄入的减少和泵出过多均可减少药物在细胞内的聚积，导致耐药。但是具体耐药机制尚不清楚。铜离子动态平衡是由铜离子转运蛋白及其分子伴侣来维持。铜离子转运蛋白家族包括铜离子转运蛋白和铜离子转运磷酸化ATP酶。本文将就铜离子转运蛋白家族与肺癌顺铂耐药作一综述。

Cisplatin is one of the most important chemotherapeutic agents, commonly used for treatment of various cancers including ovary, endometrial, lung and gastric cancer. The secondary drugresistance, however, limits the efficacy of chemotherapy and consequently compromises the prognosis of patients. Recently, there have been some important developments in the understanding of mechanisms of tumor resistance to cisplatin. One of them is concerning the association between the tumor resistance to platinum drugs and the reduced intracellular accumulation owing to impaired drug intake and enhanced outward transport. However, mechanisms for transporting platinum drugs were not known until recently studies have shown that copper transporters may be involved in the transport of platinum-based anticancer drugs. Body copper homeostasis is maintained by a group of proteins including copper transporters and chaperones. Copper transporters include copper transporter 1 and copper-transporting P-type adenosine triphosphatase. This paper will state copper ion transport protein family and cisplatin drug resistance in lung cancer.