Liubov Shimolina, Alexander Gulin, Aleksandra Khlynova, Nadezhda Ignatova, Irina Druzhkova, Margarita Gubina, Elena Zagaynova, Marina K Kuimova, Marina Shirmanova
{"title":"Development of resistance to 5-fluorouracil affects membrane viscosity and lipid composition of cancer cells.","authors":"Liubov Shimolina, Alexander Gulin, Aleksandra Khlynova, Nadezhda Ignatova, Irina Druzhkova, Margarita Gubina, Elena Zagaynova, Marina K Kuimova, Marina Shirmanova","doi":"10.1088/2050-6120/ac89cd","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":18596,"journal":{"name":"Methods and Applications in Fluorescence","volume":" ","pages":""},"PeriodicalIF":2.4000,"publicationDate":"2022-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"3","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Methods and Applications in Fluorescence","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1088/2050-6120/ac89cd","RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, ANALYTICAL","Score":null,"Total":0}
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.
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.