基于液相色谱-高分辨质谱技术的厄洛替尼获得性耐药肺腺癌细胞代谢轮廓分析

发布时间：2018-02-05 21:25

本文关键词： 厄洛替尼耐药代谢轮廓分析超高效液相色谱串联四级杆飞行时间质谱肺腺癌　出处：《上海交通大学学报(医学版)》2017年05期 　论文类型：期刊论文

【摘要】：目的·探讨表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKI)厄洛替尼耐药后人肺腺癌细胞(PC9-ER)代谢组学轮廓变化,以发现与耐药相关的差异代谢物组。方法·采用超高效液相色谱串联四级杆飞行时间质谱(UPLC-QTOF/MS)技术采集分析PC9-ER细胞及同源亲本PC9细胞的代谢轮廓,并利用偏最小二乘判别分析(PLS-DA)等多维统计手段进一步筛选、鉴定厄洛替尼耐药相关的差异代谢物。结果·与PC9细胞相比,PC9-ER细胞共有14种差异代谢物,其中N-乙酰亚精胺、磷脂酰乙醇胺、腺嘌呤核糖核苷酸、泛酸、脯氨酸、谷氨酸、组氨酸等7种代谢物水平上调,瓜氨酸、磷酸胆碱、还原型谷胱甘肽、半胱氨酰甘氨酸、氧化型谷胱甘肽、烟酰胺腺嘌呤二核苷酸、S-腺苷甲硫氨酸等7种代谢物水平下调,主要涉及谷氨酸代谢、谷胱甘肽代谢、氨循环、蛋白质生物合成等代谢通路。结论·厄洛替尼耐药后人肺腺癌细胞代谢轮廓发生改变。差异代谢物信息可为耐药新机制和代谢相关药物靶点的发现提供线索。
[Abstract]:Objective to investigate the epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) erlotinib resistant human lung adenocarcinoma cells (PC9-ER) metabonomics profile changes, differences in order to find metabolites associated with drug resistance. Methods using ultra performance liquid chromatography tandem four quadrupole time of flight mass spectrometry (UPLC-QTOF/MS) technology acquisition and analysis of metabolism the contour and homologous parental PC9 cells PC9-ER cells, and using partial least squares discriminant analysis (PLS-DA) and other multi-dimensional statistical means further screening, identification of imatinib resistance related differences of erlotinib metabolites. Results compared with PC9 cells, PC9-ER cells, a total of 14 metabolites, including N- acetylspermidine, phosphatidylethanolamine, adenine ribonucleotide, pantothenic acid, proline, glutamic acid, histidine 7 metabolites level increased, citrulline, phosphocholine, glutathione, cysteinyl glycine, oxidized Glutathione, nicotinamide adenine dinucleotide S-, S-adenosylmethionine and other 7 kinds of metabolite levels down, mainly involved in glutamate metabolism, glutathione metabolism, ammonia cycle, protein synthesis and other metabolic pathways. Conclusion erlotinib resistant human lung adenocarcinoma cell metabolic profile changes. Information can be found for different metabolites and metabolic mechanism of new drug resistance related drugs the target to provide clues.

【作者单位】：上海交通大学医学院;上海交通大学基础医学院药理学教研室;
【基金】：国家自然科学基金(81573018) 上海市青年科技英才——扬帆计划(15YF1406700)~~
【分类号】：R734.2

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