肿瘤防治研究2025,Vol.52Issue(7):554-561,8.DOI:10.3971/j.issn.1000-8578.2025.24.1125
新藤黄酸调控Wnt/β-catenin信号通路抑制结肠癌干细胞特性
Neogambogic Acid Suppresses Characteristics of Colorectal Cancer Stem Cells Through Inhibition of Wnt/β-catenin Signaling Pathway
摘要
Abstract
Objective To explore the role of neogambogic acid in the characteristics of colorectal cancer stem cells(CRC-CSCs)through the Wnt/β-catenin signaling pathway.Methods The colorectal cells SW480 and HCT166 were divided into control group and neogambogic acid groups(1.5,3,6,and 12 μmol/L).The viability of CRC-CSCs was determined by MTT method,and spheroid and clone formation assays were used to assess the capacity of spheroid formation and self-renewal ability of the cells.The effects of neogambogic acid on the apoptosis and cell cycle of CRC-CSCs were evaluated by flow cytometry assays.Real-time quantitative PCR was used to detect the mRNA expression levels of relative markers(CD133,CD44,ALDH1,Oct4,and Nanog)of CRC-CSCs,and the protein expression levels of the self-renewal marker(PCNA),apoptosis markers(cleaved caspase-3 and cleaved caspase-9),and Wnt/β-catenin signaling pathway markers(p-GSK3β,GSK3β,β-catenin,and Wnt)were analyzed using Western blot.Results Compared with the control group,after neogambogic acid treatment,the viability of SW480 and HCT116 cells decreased(P<0.05),the spheroid forming ability and the clone numbers of CRC-CSCs decreased(P<0.001,P<0.01)but the cell apoptosis rate increased(P<0.01),and cell cycle was arrested in G0/G1 phase.Moreover,neogambogic acid downregulated the mRNA and protein expression of relative markers of CRC-CSCs(CD133,CD44,ALDH1,Oct4,and Nanog),PCNA,p-GSK3β,β-catenin,and Wnt(P<0.05)and upregulated the expression of cleaved caspase-3,cleaved caspase-9,and GSK3β(P<0.01).Conclusion Neogambogic can inhibit the stem cell properties of colorectal cells via inhibition of Wnt/β-catenin signaling pathway.As a result,neogambogic acid may be an attractive agent against colorectal cancer.关键词
新藤黄酸/结肠癌/结肠癌干细胞/增殖/凋亡/Wnt/β-cateninKey words
Neogambogic acid/Colorectal cancer/Colorectal cancer stem cells/Proliferation/Apoptosis/Wnt/β-catenin分类
医药卫生引用本文复制引用
王浩,黄慧贤,李悠然,严跃华,易嘉钦,刘晓玉,罗冬梅,谷雨..新藤黄酸调控Wnt/β-catenin信号通路抑制结肠癌干细胞特性[J].肿瘤防治研究,2025,52(7):554-561,8.基金项目
Youth Project of the National Natural Science Foundation of China(No.81904204) (No.81904204)
General Project of the Medical Research Program of Jiangsu Provincial Health Commission(No.M2021061) (No.M2021061)
2023 Jiangsu Provincial Postgraduate Research and Practice Innovation Program of Nanjing University of Chinese Medicine(No.SJCX23_0902) 国家自然科学基金青年项目(81904204) (No.SJCX23_0902)
江苏省卫生健康委医学科研项目面上项目(M2021061) (M2021061)
南京中医药大学2023年江苏省研究生科研与实践创新计划项目(SJCX23_0902) (SJCX23_0902)