| 于歌,赵倩,刘云章,等.转基因斑马鱼模型应用于索拉非尼抗肝癌活性筛选的方法研究[J].中国海洋药物,2017,36(1):48-54. |
| 转基因斑马鱼模型应用于索拉非尼抗肝癌活性筛选的方法研究 |
| Application of Zebrafish Liver Tumor Model on Screening of Anti-Tumor Compounds such as Sorafenib |
| 投稿时间：2016-05-12 修订日期：2016-05-20 |
| DOI： |
| 中文关键词: 斑马鱼模型 索拉非尼 药物筛选 盐酸多西环素 肝癌 |
| English Keywords:transgenic zebrafish model sorafenib drug screening doxycycline hydrochloride liver cancer |
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| 摘要点击次数: 5079 |
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| 中文摘要: |
| 目的 使用斑马鱼 (Danio rerio) 肝癌模型进行药物筛选,确定筛选方法和最适条件。方法 用不同浓度盐酸多西环素 (Dox) 处理转基因斑马鱼胚胎,诱导其肝脏异常增生,通过综合评价诱导效应与毒性效应,确定适合的诱导浓度；选择适宜的诱导浓度,对索拉非尼抑制肝部异常增生的能力进行评估。结果 确定了盐酸多西环素的最适诱导浓度为30~60mg/L,索拉非尼对斑马鱼模型的肝部异常增生有显著的抑制作用,同时也观察到药物的毒副作用。结论 该模型适用于索拉非尼及其类似物抗肝癌活性的评价与筛选,是评估化合物体内生物活性的快速筛选模型,同时也可以观测毒副作用,在其它抗肝癌药物及与Ras下游信号通路相关靶点的药物的筛选等方面具有广阔的应用前景。 |
| English Summary: |
| Objective Establish the application of a zebrafish (Danio rerio) liver tumor model on anti-tumor drug screening with using sorafenib. Methods The fish embryos (5dpf) were treated with Dox (or Dox and sorafenib) in several concentration groups for 2 days. The liver size or fluorescence intensity and their side effects or toxicities were determined. The optimum concentration of Dox to induce liver tumors in the driver-effector double transgenic zebrafish embryos were figured out. Both anti-tumor effect and toxicities were evaluated in this model with using sorafenib. Results The optimum concentration of Dox to induce liver tumors in tested fish model are 30~60mg/L. Sorafenib suppressed liver tumorigenesis in Dox-induced zebrafish liver tumor model significantly at the lower concentration, however, showed toxicity at the higher concentrations. Conclusion This zebrafish model can provide an experimentally convenient vertebrate-based screening system for rapid drug discovery and toxicity testing in vivo. It can be used not only for the sorafenib screening, but also for the other anti-cancer drug-screening targeting to the downstream signaling pathways of Ras. |
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