关键词: 斑马鱼, 长春碱, abcb4, 多药耐药

Abstract: Objective To explore the effects of vinblastine on abcb4 tumor resistance gene expression in early development zebrafish and lay an important foundation for multi-drug resistant antineoplastic screening in zebrafish model. Methods Zebrafish embryos of 0.5~1.5 hours after fertilization(0.5~1.5 hpf) were exposured by different concentrations of vinblastine, and then calculated the IC50 of vinblastine. Zebrafish embryos of 0.5~1.5 hpf were treated with different concentrations of vinblastine and embryo culture medium respectively, and then observed zebrafish embryo development in 24~120 hpf and recorded the number of death, hatch and malformation .Evaluating the impact of vinblastine on abcb4 gene expression in zebrafish with quantitative real-time PCR and whole-mount in situ hybridization by collecting zebrafish embryos exposed to different concentrations of vinblastine. Results Vinblastine IC50 in zebrafish embryos is 3.08 ?mol/L. The mRNA level of abcb4 gene in vinblastine treated embryos was significantly increased compared to blank control group. Moreover, abcb4 gene positive hybridization signals were found in the small intestine of zebrafish embryos after 120 hpf and also partly found in the brain and heart of zebrafish embryos by the method of whole-mount in situ hybridization. Conclusions Vinblastine can significantly increase the expression level of abcb4 tumor resistancegene in early development zebrafish embryos, which points out that zebrafish can be used as a tumor resistant drug screening model.

Key words: Zebrafish, Vinblastine, abcb4, Multidrug-resistance