张亚楠1,孙继红1,黄新益2,项仪宾2,余伯阳2*.普纳替尼对人血管内皮细胞功能的影响[J].药物评价研究,2015,38():1-5
普纳替尼对人血管内皮细胞功能的影响
Effects of Ponatinib on human umbilical vein endothelial cell function in vitro
投稿时间:2014-12-04  
DOI:
中文关键词:  Ponatinib;血栓;人脐静脉内皮细胞;机制
英文关键词:Ponatinib; thrombosis; human umbilical vein endothelial cells; mechanism
基金项目:
作者单位
张亚楠1,孙继红1,黄新益2,项仪宾2,余伯阳2* 1. 中国药科大学,江苏 南京 211198
2.2. 南京圣和药业股份有限公司,江苏 南京 210038 
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中文摘要:
      目的 观察普纳替尼(Ponatinib)对人血管内皮细胞的增殖、迁移、血管形成及NO合成释放的影响,从细胞水平评价Ponatinib血栓不良反应形成机制。方法 分别采用CCK-8法、体外划痕法、Matrigel基底膜成管法及NO检测试剂盒分别考察Ponatinib对人脐静脉内皮细胞(HUVECs)的细胞毒作用、迁移能力、血管形成能力及细胞NO释放水平的影响。结果 研究表明Ponatinib对HUVECs细胞半数致死浓度(IC50)为(0.69±0.05)μmol/L。非毒性剂量的Ponatinib能够不同程度抑制HUVECs细胞的迁移、血管形成及NO的释放(P<0.05)。结论 Ponatinib通过影响人血管内皮细胞增殖、迁移、血管形成等正常功能而造成血管内皮损伤,可能为其诱发血栓的原因之一。
英文摘要:
      Objective To investigate the effect of Ponatinib on human vascular endothelial cell proliferation, migration, angiogenesis and the synthesis and release of NO and to evaluate the mechanisms of thrombotic adverse reaction of Ponatinib in vitro. Methods CCK-8 assay, wound healing test, tube formation assay, and NO detection Kit were used to investigate the cytotoxicity, migration, angiogenesis, and NO release of Ponatinib on human umbilical vein endothelial cells (HUVECs). Results It was found that the IC50 value of Ponatinib on HUVECs was (0.69 ± 0.05) μmol/L. Non-toxic concentration of Ponatinib was able to inhibit the proliferation, migration, angiogenesis, and NO release (P < 0.05). Conclusion Ponatinib may injure the vascular endothelial cells by inhibiting the proliferation, migration, angiogenesis, and other functions of human vascular endothelial cells, which might be one of the main mechanisms of thrombotic adverse reaction, so as to provide the references for future research on the thrombosis mechanisms of Ponatinib.
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