肿瘤防治研究2024,Vol.51Issue(6):402-408,7.DOI:10.3971/j.issn.1000-8578.2024.24.0121
紫草素调控Wnt/β-catenin抑制腺瘤性结肠息肉突变结肠癌细胞生长
Shikonin Inhibits APC-mutant Colon Cancer via Wnt/β-catenin Signaling
摘要
Abstract
Objective To identify small molecule inhibitors of APC-mutant colon cancer and provide lead compounds for targeted therapy of colon cancer.Methods APC-mutant colon cancer cell lines that stably express 7*Tcf-GFP/SV40-Cherry(7TGC)dual fluorescence reporter system was constructed for small-molecule inhibitor screening.Cell viability,colony formation,EdU incorporation,and xenograft tumor assay were used to evaluate the inhibitory effect of these inhibitors on APC-mutant colon cancer in vitro and in vivo.Western blot and co-immunoprecipitation assays were used to explore the molecular mechanism.Results Four small molecules that inhibited Wnt activity in APC-mutant colon cancer cells were discovered.Shikonin exhibited significant inhibition of cell viability and proliferation while inducing apoptosis of APC-mutant colon cancer cells.Xenograft tumor assay demonstrated that shikonin significantly reduced tumor growth in vivo.Furthermore,Western blot and co-immunoprecipitation assays revealed that shikonin markedly decreased β-catenin levels.Conclusion Shikonin effectively inhibits Wnt activity and suppresses tumor growth in APC-mutant colon cancer.关键词
APC突变/结肠癌/Wnt/β-catenin信号通路/紫草素Key words
APC mutation/Colon cancer/Wnt/β-catenin signaling/Shikonin引用本文复制引用
陈黎喆,王伯军,龚晴,张雪,柯细松..紫草素调控Wnt/β-catenin抑制腺瘤性结肠息肉突变结肠癌细胞生长[J].肿瘤防治研究,2024,51(6):402-408,7.基金项目
National Natural Science Foundation of China(No.82173845) 国家自然科学基金面上项目(82173845) (No.82173845)