Single-cell mass spectrometry studies of drug metabolism heterogeneity and primary resistance to gefitinib in non-small cell lung cancer cells

作     者：Guizhen Zhu Yaoyao Zhao Wenmei Zhang Yuanyuan Wu Yuanxing Liu Guangsheng Guo Xiayan Wang Zhihong Liu Guizhen Zhu;Yaoyao Zhao;Wenmei Zhang;Yuanyuan Wu;Yuanxing Liu;Guangsheng Guo;Xiayan Wang;Zhihong Liu

作者机构：Center of Excellence for Environmental Safety and Biological EffectsBeijing Key Laboratory for Green Catalysis and SeparationDepartment of ChemistryBeijing University of TechnologyBeijing 100124China Minzu University of ChinaBeijing 100081China Key Laboratory for the Synthesis and Application of Organic Functional MoleculesCollege of Health Science and EngineeringHubei UniversityWuhan 430062China 

出 版 物：《Chinese Chemical Letters》 (中国化学快报（英文版）)

年 卷 期：2024年第35卷第2期

页      面：436-440页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 081704[工学-应用化学] 07[理学] 08[工学] 0817[工学-化学工程与技术] 070302[理学-分析化学] 0703[理学-化学] 10[医学] 

基　　金：supported by the Beijing Outstanding Young Scientist Program(No.BJJWZYJH01201910005017) the National Natural Science Foundation of China(Nos.22127805 and 22206008) 

主　　题：Single-cell mass spectrometry Drug metabolism Non-small cell lung cancer Gefitinib Primary resistance 

摘      要：Patients with epidermal growth factor receptor(EGFR)wild-type non-small cell lung cancer(NSCLC)often show primary resistance to gefitinib *** is thus necessary to study the metabolism of gefitinib in NSCLC cells to comprehensively reveal the reasons for the primary resistance of ***,we develop a platform for studying drug metabolism heterogeneity based on single-cell mass spectrometry(sDMH-scMS)by integrating living-cell electrolaunching ionization MS(ILCEI-MS)and high-performance liquid chromatography-MS(HPLC-MS)analysis,and the primary resistance of NSCLC cells to gefitinib was studied using this *** ILCEI-MS analysis showed that approximately 11.9%of NSCLC single cells contained the gefitinib metabolite M11;HPLC-MS detection diluted the intensity of M11 in subpopulations and concealed the heterogeneity of drug metabolism in tumor single *** intensity of gefitinib in EGFR wild-type A549 cells was markedly lower than in mutant PC9 cells,and the intensity of gefitinib metabolites was significantly higher than in PC9 cells,suggesting that the primary resistance of NSCLC cells is related to gefitinib ***,the combination of gefitinib and the drug-metabolizing enzyme inhibitorα-naphthoflavone was shown to overcome the primary resistance of the NSCLC ***,the results of this study are expected to be applicable for clinical drug resistance diagnosis and treatment at the single-cell level.