中国海洋药物2024,Vol.43Issue(4) :67-72.

以斑马鱼模型筛选具有Wnt/β-catenin信号通路抑制活性的海洋来源化合物

Screening of marine derived Wnt/β-catenin signaling pathway inhibitors using zebrafish model

朱琳 王正阳 张祺 周建峰 荣小至 白艳
中国海洋药物2024,Vol.43Issue(4) :67-72.

以斑马鱼模型筛选具有Wnt/β-catenin信号通路抑制活性的海洋来源化合物

Screening of marine derived Wnt/β-catenin signaling pathway inhibitors using zebrafish model

朱琳 1王正阳 1张祺 1周建峰 1荣小至 1白艳1
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作者信息

  • 1. 中国海洋大学海洋药物教育部重点实验室,医药学院,山东青岛 266003
  • 折叠

摘要

目的 利用模式生物斑马鱼构建的特异激活Wnt信号通路的筛选评价体系,对海洋来源的化合物进行筛选及活性初步验证.方法 在斑马鱼原肠胚时期用Wnt/β-catenin信号通路激活剂6-bromoindirubin-3-oxime(BIO)和海洋来源化合物共同处理受精后6h(hpf)斑马鱼胚胎,48 hpf观察分析胚胎表型,并进一步结合癌细胞系进行增殖活性检测.结果 共筛选海洋来源化合物113种,其中17#、34#、42#化合物能够显著营救BIO激活Wnt/β-catenin信号通路造成的斑马鱼眼睛缺失的异常表型,且42#化合物能抑制Wnt/β-catenin高活性的结肠癌细胞的增殖.已知在许多癌症中Wnt/β-catenin信号通路异常激活,因此通过此评价体系筛选新的Wnt/β-catenin信号通路抑制剂具有重要意义.

Abstract

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.

关键词

Wnt/β-catenin信号通路/海洋来源化合物/斑马鱼

Key words

Wnt/β-catenin signaling pathway/marine-derived compounds/zebrafish

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出版年

2024
中国海洋药物
中国药学会

中国海洋药物

CSTPCDCSCD
影响因子:0.539
ISSN:1002-3461
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