The formation of intracellular nanoparticles correlates with cisplatin resistance  

顺铂治疗细胞内部铂纳米颗粒的发现及其与耐药性关系的研究（英文）

作　　者：曹萌 刘方舟 张喜全 郑明 叶子琦 常维维 吉民 詹熙 顾宁 

机构地区：[1]State Key Laboratory of Bioelectronics, School of Biological Science & Medical Engineering, Southeast University [2]School of Public Health, Southeast University [3]The Center for Inflammatory and Vascular Diseases, Department of Pathology, University of Maryland School of Medicine Baltimore [4]Department of Head and Neck Surgery, Jiangsu Cancer Hospital [5]Nanjing Chia-tai Tianqing Pharmaceutical Co. Ltd [6]College of Life and Environmental Science, Wenzhou University

出　　处：《Science China Materials》2015年第8期640-648,594,共10页中国科学（材料科学（英文版）

基　　金：Funded by the National Key Basic Research Program of China (2011CB933503);the National Natural Science Foundation of China (NSFC) for Key Project of International Cooperation (61420106012);the Special Funds of National Natural Science Foundation of China For Basic Research Projects of Scientific Instruments (61127002);the Special Project on the Development of National Key Scientific Instruments and Equipment of China (2011YQ03013403);China Postdoctoral Science Foundation funded project (2013M541592)

摘　　要：Patients treated with the cisplatin often develop strong resistance to the drug after prolonged treatments, ultimately resulting in limited clinical efficacy. One of the possible mechanisms is that the internalized compound may be inactivated before getting access to the nucleus where cisplatin forms a complex with the genomic DNA and triggers a cell death program. However, the nature and intracellular fate of inactivated cisplatin is poorly illustrated. In the present study, we reported for the first time the presence of platinum nanoparticles(Pt-NPs) in the cytoplasm of cells treated with cisplatin. Further analysis also evidenced a correlation of the increased intracellular PtNPs formation with cisplatin resistance, and confirmed the process was glutathione S-transferase relevant. Our data suggest that tumor cells may develop cisplatin resistance by converting the drug into less toxic intracellular Pt-NPs, thereby impeding the drug from targeting its substrates.长期使用顺铂治疗的肿瘤患者容易产生肿瘤细胞耐药性,影响顺铂的临床治疗效果.顺铂进入肿瘤细胞后,在到达靶向细胞核之前可能会失去活性,失活后的药物将无法与DNA络合以杀伤细胞,这是细胞产生药物耐受性的可能机制之一.然而失活后的顺铂在细胞内以何种形式存在这一问题尚没有得到完全阐明.本论文研究发现,顺铂治疗后的细胞中有铂纳米颗粒存在,而且该类颗粒的形成与细胞对顺铂的耐药性有一定的关系.进一步研究发现细胞内谷胱甘肽转移酶可能在这一机制中起到了重要作用.数据表明,细胞可能通过将高细胞毒性的顺铂转化为低毒性的铂纳米颗粒,起到阻止顺铂靶向其底物的作用.

关 键 词：顺铂 细胞 耐药性 抗药性 铂纳米颗粒 

分 类 号：R730.5[医药卫生—肿瘤]