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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 observe the effects of Ponatinib on the proliferation, migration, angiogenesis and release of nitric oxide synthase in human vascular endothelial cells. The mechanism of Ponatinib thrombus formation was evaluated at the cellular level. Methods The cytotoxicity, migration, angiogenesis and nitric oxide (NO) release of Ponatinib on human umbilical vein endothelial cells (HUVECs) were investigated by CCK-8 assay, in vitro scoring assay, Matrigel substrate tube formation assay and NO assay kit, respectively Horizontal impact. Results The results showed that the half inhibitory concentration (IC50) of Ponatinib on HUVECs was (0.69 ± 0.05) μmol / L. Non-toxic doses of Ponatinib inhibited HUVECs migration, angiogenesis and NO release to varying degrees (P <0.05). Conclusion Ponatinib may cause vascular endothelial injury by affecting the normal function of human vascular endothelial cells such as proliferation, migration and angiogenesis, which may be one of the causes of thrombosis.