RT Journal Article SR Electronic T1 Saturated Fatty Acids in Cell Membrane Lipids Induce Resistance to 5-Fluorouracil in Colorectal Cancer Cells JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 3313 OP 3324 DO 10.21873/anticanres.15819 VO 42 IS 7 A1 TAKANORI HIRAIDE A1 YOSHIFUMI MORITA A1 MAKOTO HORIKAWA A1 EIJI SUGIYAMA A1 TOMOHITO SATO A1 TOMOAKI KAHYO A1 SATORU FURUHASHI A1 MAKOTO TAKEDA A1 HIROTOSHI KIKUCHI A1 YOSHIHIRO HIRAMATSU A1 TAKANORI SAKAGUCHI A1 HIROYUKI KONNO A1 MITSUTOSHI SETOU A1 HIROYA TAKEUCHI YR 2022 UL http://ar.iiarjournals.org/content/42/7/3313.abstract AB 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. 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. 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. Conclusion: These data suggest that the saturated to monounsaturated fatty acid ratio in cellular membranous phospholipids affects sensitivity to chemotherapeutic agents.