Liquid extraction surface analysis nanospray electrospray ionization based lipidomics for in situ analysis of tumor cells with multidrug resistance
Liquid extraction surface analysis nanospray electrospray ionization based lipidomics for in situ analysis of tumor cells with multidrug resistance
复制标题
基于液体提取表面分析纳喷雾电喷雾电离的脂质组学用于多药耐药肿瘤细胞的原位分析
DOI：
10.1002/rcm.8229
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发表时间：
2018-10-15
影响因子：
2
通讯作者：
Song，Fengrui
中科院分区：
文献类型：
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作者：
Zong，Li;Pi，Zifeng;Song，Fengrui
合理的多药耐药(MDR)是肿瘤治疗中的一大挑战。细胞膜中的脂质成分和氧化还原平衡与MDR的发生发展密切相关。液萃取质谱联用技术(LESA-MS)具有样品制备少、分析速度快、灵敏度高、高通量等特点，得到了广泛的应用。方法采用LESA-MS对生长在玻片上的完整的MCF-7/ADR细胞(阿霉素耐药乳腺癌细胞)及其亲本细胞MCF-7/S细胞的脂类和其他特异性代谢产物进行现场测定，并用原子力显微镜观察提取前后肿瘤细胞的形态。采用多元统计分析研究与MDR相关的潜在脂质生物标志物。结果脂质水平的变化与MCF7/S细胞的多药耐药密切相关。此外，还观察到细胞膜流动性降低和细胞膜电位升高，从而证实了多药耐药引起的细胞膜变化。与MCF-7/S细胞相比，MCF-7/Adr细胞的GSH/GSSG、ATP/ADP、ATP/AMP比值明显升高。结论脂质成分改变导致细胞膜流动性降低，细胞膜电位升高，抗氧化能力增强，能量生成增强，参与了MDR的发生发展。这项研究中发现的具体改变可能为克服MDR提供更多信息。
RationaleMultidrug resistance (MDR) occurs frequently and is a major challenge in tumor treatment. The lipid composition in the cell membrane and the redox balance are closely associated with the development of MDR. Liquid extraction surface analysis in combination with mass spectrometry (LESA‐MS) has the characteristics of minimal sample preparation, rapid analysis, high sensitivity and high throughput, and has obtained wide applications.MethodsLESA‐MS was employed toin situdetermine the lipids and other specific metabolites of intact MCF‐7/ADR cells (adriamycin‐resistant breast cancer cells) and its parental MCF‐7/S cells grown on a glass slide.In situatomic force microscopy was used to observe the morphology of tumor cells before and after extraction. Multivariate statistical analysis was used to investigate the potential lipid biomarkers correlated with the MDR. Moreover, the cell membrane fluidity and potential were determined.ResultsThe changes in the level of the lipids were closely correlated with the multidrug resistance of MCF‐7/S cells. Moreover, lower cell membrane fluidity and higher cell membrane potential were observed and thus demonstrated the changes in the cell membrane induced by multidrug resistance. Also, the ratios of GSH/GSSG, ATP/ADP and ATP/AMP were significantly higher in MCF‐7/ADR cells relative to MCF‐7/S cells.ConclusionsLower cell membrane fluidity and higher cell membrane potential caused by the changes in lipid compositions, enhanced anti‐oxidative ability and energy generation were involved in the development of the MDR. The specific alterations identified in this study may provide more information for overcoming MDR.