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
1
;
Qing GONG
1
;
Xue ZHANG
1
;
Xisong KE
1
Author Information
1. Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
- Publication Type:SPECIALFEATURE
- 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.
