Screening of marine derived Wnt/β-catenin signaling pathway inhibitors using zebrafish model
Objective This study used a screening system based on the zebrafish model,which is specifically activated by the Wnt/β-catenin signaling pathway.Marine-derived compounds were subjected to screening,followed by preliminary validation of activity.Methods Fertilized zebrafish embryos were treated with the Wnt/β-catenin signaling pathway activator 6-bromoindirubin-3-oxime(BIO)and marine-derived compounds during gastrula period,and analyzed for embryo phenotype at 48 hour after fertilization(hpf).Further,prolif-eration activity was assessed in colon cancer cell lines with high Wnt/β-catenin activity.Results A total of 113 marine-derived compounds were screened,among which compounds 17#,34#,42# could significantly rescue the abnormal phenotype of eye loss caused by the activation of the Wnt/β-catenin signaling pathway by BIO,and compound 42# inhibited the proliferation of colon cancer cells with high Wnt/β-catenin activity.As Wnt/β-catenin signaling is abnormally activated in many cancers,screening for new inhibitors of the Wnt/β-catenin signaling pathway is of significant importance.
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