PT  - JOURNAL ARTICLE
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
TI  - Saturated Fatty Acids in Cell Membrane Lipids Induce Resistance to 5-Fluorouracil in Colorectal Cancer Cells
AID  - 10.21873/anticanres.15819
DP  - 2022 Jul 01
TA  - Anticancer Research
PG  - 3313--3324
VI  - 42
IP  - 7
4099  - http://ar.iiarjournals.org/content/42/7/3313.short
4100  - http://ar.iiarjournals.org/content/42/7/3313.full
SO  - Anticancer Res2022 Jul 01; 42
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.