[Metabolomics Study on the Differences of Endogenous Small Molecule between A549/DDP and A549 Cells Based on High Solution UPLC-TOF-MS]

Zhongguo Fei Ai Za Zhi. 2018 Aug 20;21(8):571-577. doi: 10.3779/j.issn.1009-3419.2018.08.01.
[Article in Chinese]

Abstract

Background: Cisplatin acquired resistance is a vital problem in the chemotherapy of non-small cell lung cancer, which needs to be further addressed. In recent years, obtaining drug resistant cells from cell cultivation and serving for metabolomics research to find differential metabolites and get potential biomarkers, is a good reference for clinical research and cancer treatment. This study aimed to obtain metabolite information related to cisplatin resistance through metabolomics analysis.

Methods: Metabolites were extracted from A549 cells and cisplatin resistant A549/DDP cells, and ultraperformance liquid chromatography coupled with time of flight mass spectrometry was used to perform metabolomic analysis of endogenous molecules of the two cells and obtain metabolic differences.

Results: Through data analysis, 40 metabolites were identified as differential metabolites, mainly involving phospholipids, fatty acids, amino acids and metabolites related to energy metabolism.

Conclusions: The drug resistance of A549/DDP cells may be caused by the changes of cell membrane structure and related metabolic pathways.

【中文题目:基于高分辨UPLC-TOF-MS探讨A549/DDP 与A549细胞内源性小分子代谢差异】 【中文摘要:背景与目的 顺铂获得性耐药是非小细胞肺癌(non-small cell lung cancer, NSCLC)化疗中至关重要并且有待进一步解决的问题。近年来通过细胞培养获得肿瘤耐药细胞,并将其作为代谢组学研究对象,寻找差异代谢物,获得潜在生物标志物,可以有效地为临床研究和治疗提供参考。本研究旨在通过代谢组学分析获取与顺铂耐药性相关的代谢物信息。方法 培养NSCLC细胞A549与其顺铂获得性耐药细胞A549/DDP后进行代谢物提取,通过超高效液相色谱-飞行时间质谱法对两种细胞的内源性小分子进行代谢组学分析,获取代谢差异物。结果 通过数据分析处理,获得40种差异代谢物,主要涉及磷脂、脂肪酸、氨基酸和能量代谢相关代谢物。结论 A549/DDP细胞的耐药性可能由于细胞膜结构的改变以及相关代谢途径的变化而导致。】 【中文关键词:肺肿瘤;耐药性;顺铂;代谢组学】.

Keywords: Chemoresistance; Cisplatin; Lung neoplasms; Metabolomics.

MeSH terms

  • A549 Cells
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Chromatography, High Pressure Liquid
  • Drug Resistance, Neoplasm
  • Humans
  • Lung Neoplasms / pathology*
  • Mass Spectrometry
  • Metabolomics / methods*

Grants and funding

本研究受国家自然科学基金项目(No.81573658)资助