| 朱琳,王正阳,张祺,等.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[J].中国海洋药物,2024,43(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 |
| 投稿时间：2023-03-22 修订日期：2023-05-06 |
| DOI：10.13400/j.cnki.cjmd.2024.04.005 |
| 中文关键词: Wnt/β-catenin信号通路 海洋来源化合物 斑马鱼 |
| English Keywords:Wnt/β-catenin signaling pathway Marine-derived compounds zebrafish. |
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| 中文摘要: |
| 目的 Wnt/β-catenin信号通路在进化上高度保守,调控多种生理进程。Wnt/β-catenin信号通路的异常激活与肿瘤的发生发展密切相关。为筛选高效、特异靶向Wnt/β-catenin信号通路抑制活性的先导化合物,本研究利用基于模式生物斑马鱼构建的特异激活Wnt信号通路的快速、直观筛选评价体系,针对海洋来源的化合物进行批量活性筛选和体内毒性评价,并进行了活性初步验证。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6小时(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。 |
| English Summary: |
| Objective The Wnt/β-catenin signaling pathway is evolutionarily conserved pathway and regulates various physiological processes. Aberrant activation of Wnt/β-catenin signaling pathway is closely related to tumor development and progression. To screen for highly effective and specific inhibitors of the Wnt/β-catenin signaling pathway, this study used a fast and intuitive screening system based on the zebrafish model, which is specifically to activated by the Wnt/β-catenin signaling pathway. Marine-derived compounds were subjected to batch activity screening and in vivo toxicity evaluation, 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, proliferation 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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