乳腺癌细胞系MCF-7中阿霉素的代谢物分析  

Analysis of metabolites of doxorubicin in breast cancer cell line MCF-7

作　　者：陈雨蕉 惠人杰 王叙 朱景宇 贾磊 金坚 陈蕴 CHEN Yu-jiao;HUI Ren-jie;WANG Xu;ZHU Jing-yu;JIA Lei;JIN Jian;CHEN Yun(School of Medicine and Pharmaceutics,Jiangnan University,Wuxi Jiangsu 214122,China)

机构地区：[1]江南大学药学院药物设计与分子药理研究室,江苏无锡214122

出　　处：《中国药理学通报》2021年第9期1271-1277,共7页Chinese Pharmacological Bulletin

基　　金：江苏省临床医学科技专项(No BL2014019);国际(地区)合作与交流项目(No 81361168001);2015年度江苏高校优秀科技创新团队计划。

摘　　要：目的研究乳腺癌靶细胞MCF-7对阿霉素的处置,为解释抗肿瘤药物药理及其副作用机制提供参考。方法选择阿霉素适应症乳腺癌的耐药细胞系MCF-7/DOX为材料,建立超高效液相色谱-四级杆串联飞行时间高分辨率质谱法(UPLC-Q-TOF-MS/MS)分析靶细胞对阿霉素的处置。结果发现两种未曾报道的微量阿霉素代谢物,通过四级杆串联飞行时间质谱推导出其结构,计算机模拟分子对接显示其对DNA的亲和力相比阿霉素均下降。结论靶细胞对阿霉素具有独特且多样的药物代谢途径,可能与阿霉素耐药机制有关联。Aim To investigate the intracellular disposition process of doxorubicin(DOX)in human breast cancer MCF-7,providing reference for explaining the pharmacology and their side effects of anti-tumor drugs.Methods The drug-resistant cell line MCF-7/DOX of breast cancer with DOX indication was selected as the material,and ultra-high performance liquid chromatography quadrupole tandem time-of-flight high-resolution mass spectrometry(UPLC-Q-TOF-MS/MS)method was established to analyze the disposal of DOX by target cells.Results Two unreported trace amounts of new metabolites of doxorubicin were found,and their structures were deduced by high-resolution multistage mass spectrometry.Molecular docking showed that its affinity for DNA was lower than that of DOX.Conclusion Target cells have unique and diverse drug metabolism pathways for DOX,which may be related to drug resistance mechanisms.

关 键 词：阿霉素 靶细胞代谢 超高效液相色谱-四级杆串联飞行时间质谱法 耐药 MCF-7 

分 类 号：R446.9[医药卫生—诊断学] R737.9[医药卫生—临床医学]