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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。
Objective To screen drug using Danio rerio liver cancer model to determine the screening method and optimal conditions. Methods Transgenic zebrafish embryos were treated with different concentrations of doxorubicin hydrochloride (Dox) to induce abnormal liver proliferation. The induction effect and toxicity effect were evaluated synthetically to determine the suitable concentration. The optimal concentration of sorafenib The ability to inhibit abnormal liver proliferation was evaluated. The results showed that the optimum concentration of doxycycline hyclate was 60mg / L, sorafenib significantly inhibited the abnormal proliferation of liver in zebrafish model, and the side effects of the drug were also observed. Conclusion This model is suitable for the evaluation and screening of sorafenib and its analogues against liver cancer. It is a rapid screening model to evaluate the biological activity of sorafenib in vivo. At the same time, the model can be used to observe the side effects of other drugs against liver cancer and the downstream signaling pathway Related targets of drug screening has broad application prospects.