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

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.