Back to Search
Start Over
Saturated Fatty Acids in Cell Membrane Lipids Induce Resistance to 5-Fluorouracil in Colorectal Cancer Cells.
- Source :
-
Anticancer research [Anticancer Res] 2022 Jul; Vol. 42 (7), pp. 3313-3324. - Publication Year :
- 2022
-
Abstract
- Background/aim: Resistance to chemotherapy is a major obstacle for patients with unresectable colorectal cancer (CRC); however, the factors that induce chemoresistance have not been elucidated. Lipid composition influences neoplastic behaviour. Therefore, this study examined whether lipid composition affects sensitivity to chemotherapeutic agents in CRC.<br />Materials and Methods: We performed a lipidomic analysis of a CRC xenograft-derived spheroid model to identify potential relationships between the lipid profile and chemoresistance to 5-fluorouracil (5-FU). Genetic and pharmacological modulation of lipid synthesis were also used in the HCT-116 and DLD-1 CRC cell lines to further characterize resistance to 5-FU.<br />Results: Our lipidomic profiling revealed that phospholipids with saturated fatty acids (SFAs) were more abundant in 5-FU-resistant spheroids. The importance of phospholipids containing SFA in chemoresistance was confirmed by showing that in HCT-116 and DLD-1 cells, genetic or pharmacological inactivation of stearoyl-CoA desaturase-1, a key enzyme that converts SFAs to monounsaturated fatty acids, increased the proportion of SFAs in membranous phospholipids and reduced cell membrane fluidity, and this ultimately resulted in resistance to 5-FU.<br />Conclusion: These data suggest that the saturated to monounsaturated fatty acid ratio in cellular membranous phospholipids affects sensitivity to chemotherapeutic agents.<br /> (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)
Details
- Language :
- English
- ISSN :
- 1791-7530
- Volume :
- 42
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Anticancer research
- Publication Type :
- Academic Journal
- Accession number :
- 35790250
- Full Text :
- https://doi.org/10.21873/anticanres.15819