中国癌症防治杂志2026，Vol.18Issue(4)：445-454,10.DOI:10.27054/j.cnki.ISSN.1674-5671.2026.04.07
奥沙利铂耐药结直肠癌细胞脂质代谢重编程特征及差异代谢物筛选
Lipid metabolic reprogramming and differential metabolite screening in oxaliplatin-resistant colorectal cancer cells
摘要
Abstract
Objective To examine the characteristics of lipid metabolic reprogramming in oxaliplatin-resistant human colorectal cancer cell line HCT116/L,screen for differential lipid molecules associated with drug resistance,and evaluate their potential biological functions.Methods The parental HCT116 cell line and its oxaliplatin-resistant derivative,HCT116/L,were used as the cell models.Oxaliplatin sensitivity was assessed by CCK-8 assay,and the resistance index(RI)was calculated.Cell migration,invasion,and clonogenic capacity were assessed via scratch wound healing,Transwell invasion,and in vitro cell colony formation assays,respectively.Untargeted lipidomics based on ultra performance liquid chromatography-andem mass spectrometry(UPLC-MS/MS)was performed to profile the lipidomes of the two cell groups.Following data preprocessing,differential lipid molecules were identified.Pathway enrichment analysis was per-formed using the Kyoto Encyclopedia of Genes and Genomes(KEGG)database.Results The RI of HCT116/L cells for oxaliplatin was determined to be 9.8.The wound healing rate,number of invaded cells,and colony-forming ability of HCT116/L cells were significantly higher than those of parental HCT116 cells(all P<0.001).Lipidomic analysis identified a total of 81 differential lipid molecules,which were predominantly associated with glycerophospholipid metabolism,choline metabolism in cancer,and sphingolipid signaling path-way.The sphingolipid metabolism and necroptosis pathways showed the highest absolute differential abundance scores,while drug re-sistance-related pathways,including autophagy and EGFR tyrosine kinase inhibitor resistance,also exhibited significant directional per-turbations.Conclusions Oxaliplatin resistance in colorectal cancer is accompanied by significant lipid metabolic reprogramming.Ab-errant glycerophospholipid and sphingolipid metabolism,along with autophagy pathway activation,may contribute to drug resistance.The identified drug resistance-associated differential lipid molecules hold promise as potential biomarkers for resistance monitoring.关键词
结直肠癌细胞/奥沙利铂/药物耐受性/脂质代谢/非靶向脂质组学Key words
Colorectal cancer cells/Oxaliplatin/Drug tolerance/Lipid metabolism/Untargeted lipidomics分类
医药卫生引用本文复制引用
廉富伟,谢丽叶,吴雪菲,胡榜利,宁淑芳..奥沙利铂耐药结直肠癌细胞脂质代谢重编程特征及差异代谢物筛选[J].中国癌症防治杂志,2026,18(4):445-454,10.基金项目
国家自然科学基金地区科学基金项目(82160446 （）
82260580) （）
广西自然科学基金面上项目(2025GXNSFAA069580 （）
2025GXNSFAA069082) （）
广西医科大学青年基金项目(GXMUYSF202449) （GXMUYSF202449）
