南方医科大学学报2026,Vol.46Issue(4):825-837,13.DOI:10.12122/j.issn.1673-4254.2026.04.11
化结消瘤方中的熊果酸通过诱导铜死亡抑制结直肠癌细胞生长
Ursolic acid in Huajie Xiaoliu Formula inhibits colorectal cancer cell growth by inducing cuproptosis
摘要
Abstract
Objective To investigate the molecular mechanism by which Huajie Xiaoliu Formula(HJF)and its active component ursolic acid inhibit colorectal cancer(CRC)cell growth.Methods Proteomics was used to analyze the effect of HJF on protein expression profile in CRC xenografts from tumor-bearing nude mice.Serum pharmacochemistry was used to identify the potential active components of HJF.Network pharmacology and molecular docking were employed to predict the interaction between ursolic acid and cuproptosis-related targets.Cellular assays including MTT,wound healing,colony formation,and Western blotting were used to validate the effects of ursolic acid on proliferation,migration,and cuproptosis-related indicators(FDX1,SLC31A1,DLAT,GSH,MDA,pyruvic acid,and Cu²⁺)in HCT-116 and LoVo cells.Results HJF regulated 628 differentially expressed proteins in CRC,involving pathways related to inflammation,immunity,and metabolism.Ursolic acid was identified as a major blood component of HJF and exhibited a strong binding affinity with the key cuproptosis protein FDX1(LiDock Score106.813).In HCT-116 and LoVo cells,ursolic acid significantly inhibited cell proliferation and migration,induced intracellular accumulation of Cu²⁺,MDA and pyruvic acid,reduced GSH levels,inhibited cellular DLAT expression,and up-regulated the expressions of FDX1 and SLC31A1.Conclusion As one of the key active components in the HJF,ursolic acid inhibits CRC cell growth by inducing cuproptosis via targeting FDX1.关键词
熊果酸/结直肠癌/铜死亡/化结消瘤方Key words
ursolic acid/colorectal cancer/cuproptosis/Huajie Xiaoliu Formula引用本文复制引用
金成桓,洪宗超,段雪云,范恒,杨晶鑫,秦佳美,邹丽艳,覃孟渊..化结消瘤方中的熊果酸通过诱导铜死亡抑制结直肠癌细胞生长[J].南方医科大学学报,2026,46(4):825-837,13.基金项目
国家自然科学基金(82505189) (82505189)
国家重点研发计划中医药现代化重点专项(2025YFC3508502) (2025YFC3508502)
湖北省自然科学基金(2023AFD067) (2023AFD067)
湖北省教育厅科学研究计划青年人才项目(Q20231904) Supported by National Natural Science Foundation of China(82505189). (Q20231904)