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细胞半数抑制浓度(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。
Objective To investigate the effect of Ponatinib on human vascular endothelial ceU proliferation, migration, anglogenesis 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 ICs0 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.
出处
《药物评价研究》
CAS
2015年第2期156-160,共5页
Drug Evaluation Research
