DOX-MNPs抑制秀丽线虫ras原癌基因的过度激活及毒性研究
首发时间:2016-01-08
摘要:目的:以秀丽隐杆线虫为模型评价阿霉素磁性纳米颗粒(doxorubicin-magnetic nanoparticles, DOX-MNPs)潜在的抗肿瘤活性及其毒性。方法:对DOX-MNPs的形态结构和磁学性能进行研究,并采用秀丽线虫ras原癌基因过度激活突变体作为实验模型,检测DOX、MNPs和DOX-MNPs对秀丽线虫ras过度激活突变体多阴门表型的抑制作用以及对咽泵速率和体长的影响。结果:DOX-MNPs形状为球形,大小均匀,平均粒径10.5±0.5 nm,具有超顺磁性和良好的磁定位性能。低浓度(5 μg/mL)DOX-MNPs即显著抑制秀丽线虫突变体MT2124的多阴门表型,而更高浓度(20 μg/mL)DOX才具有相近的效果。DOX显著降低秀丽线虫咽泵速率,而DOX-MNPs对线虫咽泵速率几乎没有影响;DOX-MNPs对线虫体长的抑制作用明显小于DOX。结论:DOX-MNPs磁学性能良好,且低浓度下即可显著抑制秀丽线虫突变体ras原癌基因的过度激活,毒性显著低于DOX,表明DOX与MNPs偶连后,极大地提高了DOX的疗效,同时有效降低了DOX的毒性。
关键词: 药理学 秀丽隐杆线虫 阿霉素磁性纳米颗粒 抗肿瘤 毒性
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DOX-MNPs suppress gain-of-fuction of ras proto-oncogene in Caenorhabditis elegans and their toxicity
Abstract:Objective: Using Caenorhabditis elegans as a model organism to evaluate the potential antitumor activity and toxicity of doxorubicin-magnetic nanoparticles (DOX-MNPs). Methods: The structure and magnetic propertiesits of DOX-MNPs were described. The influences of DOX, MNPs and DOX-MNPs on the multivulva (Muv) phenotype, pharyngeal pumping rate and body length of ras(gf) mutant were evaluated. Results: The DOX-MNPs were spherical and the grain sizes distribution were homogeneous with an average particle diameter of 10.5±0.5 nm, showing excellent superparamagnetic and magnetotactic. DOX-MNPs with low concentrations (5 μg/mL) could significantly suppress the Muv phenotype of MT2124, While higher concentration (20 μg/mL) of DOX showed a similar effect. DOX significantly decreased the pharyngeal pumping rate of worms, DOX-MNPs had little impact on pharyngeal pumping rate. Moreover, DOX-MNPs had lower influence on the body length of the MT2124 compared with DOX. Conclusion: DOX-MNPs with excellent magnetic properties could effectively inhibit the excessive activation of ras gene at low concentrations and showed the lower toxicity. Our results indicated that when DOX was conjugated to MNPs, DOX-MNPs were more efficient and of lower toxicity than single DOX.
Keywords: pharmacology C.elegans DOX-MNPs anti-tumor toxicity
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DOX-MNPs抑制秀丽线虫ras原癌基因的过度激活及毒性研究
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