文章摘要
苗 丽,黄 茂,姚 欣,杜 强,李丽丽.sunitinib对气道平滑肌细胞增殖和迁移的影响及机制[J].南京医科大学学报,2010,(5):579~585
sunitinib对气道平滑肌细胞增殖和迁移的影响及机制
The effect and mechanisms of sunitinib on airway smooth cells proliferation and migration
  
DOI:10.7655
中文关键词: 气道平滑肌细胞  sunitinib  血小板源性生长因子BB  细胞增殖  细胞迁移
英文关键词: smooth muscle cell  sunitinib  platelet-derived growth factor-BB  cell proliferation  cell migration
基金项目:国家自然科学基金资助(30700342)
作者单位
苗 丽 南京医科大学第一附属医院呼吸科,江苏 南京 210029 
黄 茂  
姚 欣  
杜 强  
李丽丽  
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中文摘要:
      目的:探讨sunitinib(sunitinib malate)对血小板源性生长因子BB(PDGF-BB)刺激的人气道平滑肌细胞(human airway smooth muscle cell,HASMCs)增殖和迁移的影响及其机制?方法:体外培养HASMCs分为:对照组?PDGF-BB组?PDGF-BB与sunitinib干预组?sunitinib组,四甲基偶氮唑蓝(MTT)微量比色法测定HASMCs增殖,流式细胞术检测HASMCs细胞周期,改良的Boyden微孔膜双槽法观察细胞迁移,Western blot检测PDGFR-β和AKT的磷酸化?结果:与对照组相比,PDGF-BB(20 ng/ml)显著诱导HASMCs的增殖和迁移(P < 0.05),sunitinib(0.3~9.0 nmol/L)呈浓度依赖性抑制PDGF-BB诱导的HASMCs增殖和迁移;PDGF-BB(20 ng/ml)刺激HASMCs后,细胞周期S期比例显著高于对照组(P < 0.05),PDGF-BB与sunitinib干预组细胞周期S期比例低于PDGF-BB组(P < 0.05);PDGF-BB组PDGFR-β和AKT的磷酸化水平较对照组为高(P < 0.05),PDGF-BB与sunitinib干预组其表达量低于PDGF-BB组?结论:sunitinib抑制PDGF-BB诱导的HASMCs增殖和迁移,可能是通过调节PI3K/AKT通路起作用?
英文摘要:
      Objective:To investigate the effect and mechanisms of sunitinib on PDGF-BB-induced proliferation and migration of human airway smooth muscle cells (HASMCs). Methods:HASMCs derived from human bronchus were divided into four groups:normal group,PDGF-BB group,PDGF-BB and sunitinib intervention group,sunitinib group. Proliferation was measured by MTT. Cell cycle progression was analyzed by flow cytometry. Migration was examined using Boyden chamber apparatus. The protein expressions of p-PDGFR-βand p-AKT were determined by western blot analysis. Results:PDGF-BB(20 ng/ml) significantly induced proliferation and migration of HASMCs as compared to controls. Sunitinib(0.3~9 nmol/L) inhibited the HASMCs proliferation and migration in response to PDGF-BB (20 ng/ml). Flow cytometry disclosed that PDGF-BB(20 ng/ml) increased significantly HASMCs ratio in S phase(P < 0.05);Sunitinib decreased HASMCs in S phase stimulated by PDGF-BB(P < 0.05). The phosphorylated protein levels of PDGFR-β and AKT in PDGF-BB group were higher than those of the normal group (P < 0.05),but were decreased in PDGF-BB and sunitinib intervention group compared with control(P < 0.05). Conclusion:It appears that sunitinib can directly inhibit PDGF-BB induced HASMCs proliferation and migration through the modulation of the PI3K/Akt pathway.
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