实用临床医药杂志2026，Vol.30Issue(9)：29-36,8.DOI:10.7619/jcmp.20260217
丁酸钠通过铁自噬增强5-氟尿嘧啶对结直肠癌细胞的杀伤作用及其分子机制研究
Sodium butyrate enhances the cytotoxic effect of 5-fluorouracil on colorectal cancer cells via ferritinophagy and its underlying molecular mechanism
摘要
Abstract
Objective To investigate whether sodium butyrate(NaB)enhances the cytotoxic effect of 5-fluorouracil(5-FU)on colorectal cancer(CRC)cells by inducing ferritinophagy,and to elucidate the underlying molecular mechanisms.Methods Human colorectal cancer cell line HCT-116 was used and divided into control group,NaB group,5-FU group,NaB+5-FU group,and NaB+5-FU+deferoxamine(DFO,iron chelator)group.After 24 h of treatment,cell viability was assessed by CCK-8 assay;long-term proliferative capacity was evaluated by colony formation assay;apoptosis rate was determined by Annexin V-FITC/PI flow cytometry;intracellular reactive oxygen species(ROS)and ferrous iron(Fe2+)levels were detected using DCFH-DA and FerroOrange fluorescent probes,respectively;expression of ferritinophagy-related proteins[nuclear receptor coactivator 4(NCOA4),ferritin heavy chain(FTHl)]and autophagy marker[microtubule-associated protein 1 light chain 3(LC3)]was examined by Western blot.Results Compared with the control group,NaB group,and 5-FU group,the NaB+5-FU group showed significantly decreased cell viability and colony formation ability,increased apoptosis rate,elevated ROS and Fe2+relative fluorescence intensi-ty,upregulated NCOA4 and LC3-Ⅱ protein expression,downregulated LC3-Ⅰ and FTH1 protein expression,and increased ratio of LC3-Ⅱ to LC3-Ⅰ(P＜0.05),indicating robust activation of the ferritinophagy pathway by the combination treatment.Following DFO intervention,the aforementioned molecular alterations and cellular phenotypes(including suppressed viability,enhanced apoptosis,and oxida-tive stress)in the NaB+5-FU+DFO group were partially reversed compared with the NaB+5-FU group(P＜0.05).Conclusion NaB may enhance the antiproliferative and proapoptotic effects of 5-FU on CRC cells by activating NCOA4-mediated ferritinophagy,promoting Fe2+release and ROS accumulation,thereby providing experimental evidence for the potential application of NaB as a che-mosensitizer.关键词
丁酸钠/5-氟尿嘧啶/结直肠癌/铁自噬/活性氧/铁死亡/细胞凋亡/化疗增敏Key words
sodium butyrate/5-fluorouracil/colorectal neoplasms/ferritinophagy/reactive ox-ygen species/ferroptosis/apoptosis/chemosensitization分类
医药卫生引用本文复制引用
陆莹莹,温东朋,夏晓博,谢雅,闫文锋..丁酸钠通过铁自噬增强5-氟尿嘧啶对结直肠癌细胞的杀伤作用及其分子机制研究[J].实用临床医药杂志,2026,30(9):29-36,8.基金项目
2024年度河南省自然科学基金项目(242300420411) （242300420411）
