TY - JOUR T1 - Saturated Fatty Acids in Cell Membrane Lipids Induce Resistance to 5-Fluorouracil in Colorectal Cancer Cells JF - Anticancer Research JO - Anticancer Res SP - 3313 LP - 3324 DO - 10.21873/anticanres.15819 VL - 42 IS - 7 AU - TAKANORI HIRAIDE AU - YOSHIFUMI MORITA AU - MAKOTO HORIKAWA AU - EIJI SUGIYAMA AU - TOMOHITO SATO AU - TOMOAKI KAHYO AU - SATORU FURUHASHI AU - MAKOTO TAKEDA AU - HIROTOSHI KIKUCHI AU - YOSHIHIRO HIRAMATSU AU - TAKANORI SAKAGUCHI AU - HIROYUKI KONNO AU - MITSUTOSHI SETOU AU - HIROYA TAKEUCHI Y1 - 2022/07/01 UR - http://ar.iiarjournals.org/content/42/7/3313.abstract N2 - 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. ER -