Development of resistance to 5-fluorouracil affects membrane viscosity and lipid composition of cancer cells.

IF 2.4 3区 化学 Q3 CHEMISTRY, ANALYTICAL
Liubov Shimolina, Alexander Gulin, Aleksandra Khlynova, Nadezhda Ignatova, Irina Druzhkova, Margarita Gubina, Elena Zagaynova, Marina K Kuimova, Marina Shirmanova
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引用次数: 3

Abstract

The investigations reported here were designed to determine whether the bulk plasma membrane is involved in mechanisms of acquired resistance of colorectal cancer cells to 5-fluorouracil (5-FU). Fluorescence lifetime imaging microscopy (FLIM) of live cultured cells stained with viscosity-sensitive probe BODIPY 2 was exploited to non-invasively assess viscosity in the course of treatment and adaptation to the drug. In parallel, lipid composition of membranes was examined with the time-of-flight secondary ion mass spectrometry (ToF-SIMS). Our results showed that a single treatment with 5-FU induced only temporal changes of viscosity in 5-FU sensitive cells immediately after adding the drug. Acquisition of chemoresistance was accompanied by persistent increase of viscosity, which was preserved upon treatment without any changes. Lipidomic analysis revealed that the resistant cells had a lower level of monounsaturated fatty acids and increased sphingomyelin or decreased phosphatidylcholine in their membranes, which partly explain increase of the viscosity. Thus, we propose that a high membrane viscosity mediates the acquisition of resistance to 5-FU.

5-氟尿嘧啶耐药性的发展影响癌细胞的膜粘度和脂质组成。
本文报道的研究旨在确定大块质膜是否参与结直肠癌细胞对5-氟尿嘧啶(5-FU)获得性耐药的机制。利用黏度敏感探针BODIPY 2染色的活培养细胞的荧光寿命成像显微镜(FLIM)来无创评估治疗过程中的黏度和对药物的适应。同时,用飞行时间二次离子质谱法(ToF-SIMS)检测膜的脂质组成。我们的研究结果表明,单次用5-FU处理药物后,5-FU敏感细胞的黏度仅在时间上发生变化。耐药的获得伴随着黏度的持续增加,黏度在处理后保持不变,没有任何变化。脂质组学分析显示,耐药细胞的单不饱和脂肪酸水平较低,膜鞘磷脂增加或磷脂酰胆碱减少,这在一定程度上解释了黏度增加的原因。因此,我们提出高膜粘度介导对5-FU的抗性获得。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Methods and Applications in Fluorescence
Methods and Applications in Fluorescence CHEMISTRY, ANALYTICALCHEMISTRY, PHYSICAL&n-CHEMISTRY, PHYSICAL
CiteScore
6.20
自引率
3.10%
发文量
60
期刊介绍: Methods and Applications in Fluorescence focuses on new developments in fluorescence spectroscopy, imaging, microscopy, fluorescent probes, labels and (nano)materials. It will feature both methods and advanced (bio)applications and accepts original research articles, reviews and technical notes.
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