吉非替尼通过抑制EGFR磷酸化特异性地抑制大鼠血管平滑肌细胞的增殖  

Gefitinib specifically inhibite vascular smooth muscle cells proliferation by supressing EGFR phosphorylation

作　　者：罗健[1] 肖婷[1] 王苏燕[1] 李芳[1] 吴志雄[1] 曾欧[1] 杨军[1] 

机构地区：[1]南华大学第一附属医院心内科,湖南衡阳421001

出　　处：《临床心血管病杂志》2015年第3期331-333,共3页Journal of Clinical Cardiology

基　　金：国家自然科学基金(No:81270181);湖南省自然科学基金(No:11JJ2046)

摘　　要：目的:探讨吉非替尼对血管平滑肌细胞(VSMC)及内皮细胞(EC)增殖的不同作用,及其与表皮生长受体因子(EGFR)磷酸化的关系。方法:分别用不同浓度的吉非替尼及紫杉醇,干预VSMC或EC不同时间后,溴化四甲基偶氮唑蓝(MTT)法测定细胞增殖抑制率;免疫印迹法(western-blotting)检测2种细胞表面EGFR表达水平及药物干预后EGFR、磷酸化EGFR(p-EGFR)表达的变化。结果:吉非替尼及紫杉醇均对VSMC的增殖有抑制作用,并具时间-剂量依赖性,吉非替尼在不同时间点对EC增殖的抑制作用均明显弱于紫杉醇。EGFR在VSMC上表达明显高于EC,在吉非替尼作用下,VSMC的EGFR蛋白磷酸化明显受到抑制。结论:吉非替尼与紫杉醇相比可更特异性地抑制VSMC的增殖,而对EC的细胞毒性作用低于紫杉醇,其机制可能与VSMC和EC表面EGFR表达水平的差异有关;吉非替尼抑制VSMC的增殖可能与其抑制EGFR磷酸化有关。Objective：To investigate the influence of gefitinib on vascular smooth muscle cells（VSMCs）and endothelial cells（ECs）proliferation.Method：Cultured VSMCs and ECs were respectively treated with different concentrations and durations of gefitinib and paclitaxel.MTT method was used to measure the influence of these two drugs on VSMCs and ECs proliferation,then calculate the growth inhibition rate,respectively.Western blot was used to determine the expression of EGFR and p-EGFR.Result：1Gefitinib and paclitaxel inhibited the proliferation of VSMCs and ECs in time-does ependence.Compared to paclitaxel,the same low concentrations of gefitinib had a comparable inhibition rate on smooth muscle cells at the same duration,but with the increase of concentration and extension of time,the inhibition rate of gefitinib increased significantly,and even exceeded paclitaxel.In addition,the inhibition of gefitinib on ECs was lower than paclitaxel with the same concentration in the same time period.2EGFR expressed in both of the two cell lines,but it expressed much higher in VSMC than in EC.Expression of p-EGFR in VSMCs was significantly suppressed after the role of gefitinib.Conclusion：Gefitinib and paclitaxel had a comparable suppression effects on VSMCs proliferation,the inhibition of Gefitinib group on ECs proliferation was obviously weaker than paclitaxel group.So it provided a theoretical and experimental basis for the application of Gefitinib in the treatment of restenosis and thrombosis after PCI.

关 键 词：吉非替尼 紫杉醇 平滑肌细胞 内皮细胞 表皮生长因子受体 磷酸化 

分 类 号：R446.61[医药卫生—诊断学]