Metabolomics analysis of multidrug-resistant breast cancer cells in vitro using methyl-tert-butyl ether method.

Metabolomics analysis of multidrug-resistant breast cancer cells in vitro using methyl-tert-butyl ether method.
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甲基叔丁基醚法对多重耐药乳腺癌细胞的体外代谢组学分析

DOI:
10.1039/c7ra12952a
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发表时间:
2018-04-23
期刊:
影响因子:
3.9
通讯作者:
Song, Fengrui
Song, Fengrui
中科院分区:
化学3区
文献类型:
--
作者:
Zong, Li;Pi, Zifeng;Liu, Shu;Liu, Zhiqiang;Song, Fengrui

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代谢组和脂质组的综合表征用于揭示未知病理状况,正被用于研究癌症的分子机制,特别是在早期诊断、治疗和预后领域。肿瘤细胞的多药耐药性(MDR)限制了抗癌药物的治疗效果,是化疗的主要障碍。在此,我们采用一种基于甲基叔丁基醚(MTBE)的提取方法,通过超高效液相色谱 - 四极杆飞行时间质谱联用技术,同时提取小极性分子和亲脂性代谢物,用于多药耐药乳腺癌细胞系MCF - 7/ADR及其亲本细胞系MCF - 7/S的非靶向代谢组学研究。基于多变量分析,MCF - 7/ADR细胞和MCF - 7/S细胞之间显示出明显不同的代谢特征。鉴定出17种潜在生物标志物,这些潜在生物标志物主要与细胞膜脂质组成、脂质调节的细胞信号传导以及抗氧化能力相关。通过原位原子力显微镜(AFM)对细胞超微结构和形态的研究也表明细胞膜随着多药耐药性而发生变化。我们期望这项研究能够为临床化疗期间监测耐药性提供一种新方法,并有助于开发克服多药耐药性的药物。 基于MTBE的细胞脂质组学用于研究乳腺癌多药耐药机制
The comprehensive characterization of metabolome and lipidome to reveal unknown pathological conditions, are being used to investigate the molecular mechanisms of cancer, especially in the field of early diagnosis, treatment, and prognosis. The multidrug resistance (MDR) of tumor cells limits the therapeutic effect of anti-cancer drugs and is the main obstacle for chemotherapy. Here, we adopted a methyl-tert-butyl ether (MTBE)-based extraction method to simultaneously extract small polar molecules and lipophilic metabolites for nontargeted metabolomics of multidrug-resistant breast cancer cell line MCF-7/ADR and its parental cell line MCF-7/S by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Distinctly different metabolic features were shown between MCF-7/ADR cells and MCF-7/S on the basis of multivariate analyses. 17 potential biomarkers were identified. And these potential biomarkers were mainly correlated with cell membrane lipids composition, cell signaling regulated by lipids, and anti-oxidation ability. The studies of cellular ultrastructure and morphology by in situ atomic force microscopy (AFM) also demonstrated the cellular membrane changed along with the MDR. We expect that this study could provide a new method for monitoring drug resistance during clinical chemotherapy and be useful for the development of drugs to overcome the MDR. MTBE-based cellular lipidomics to investigate the mechanisms of multidrug resistance of breast cancer.
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发表时间: 2015-01-01
影响因子: 2.8
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发表时间: 2017-03-01
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影响因子: 3.6
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发表时间: 2008-05-01
影响因子: 6.5
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