Shikonin Inhibits APC-mutant Colon Cancer via Wnt/β-catenin Signaling
10.3971/j.issn.1000-8578.2024.24.0121
- VernacularTitle: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
- Author:
Lizhe CHEN
1
;
Bojun WANG
;
Qing GONG
;
Xue ZHANG
;
Xisong KE
Author Information
1. 201203 上海,上海中医药大学交叉科学研究院化学生物研究中心
- Keywords:
APC mutation;
Colon cancer;
Wnt/β-catenin signaling;
Shikonin
- From:
Cancer Research on Prevention and Treatment
2024;51(6):402-408
- CountryChina
- Language:Chinese
-
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.
