sunitinib对人气道平滑肌细胞增殖?迁移和ERK磷酸化的影响
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The effect of sunitinib on the proliferation, migration and phosphorylation of ERK of human airway smooth cell
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    目的:探讨sunitinib对血小板源性生长因子(platelet-derived growth factor,PDGF)-BB刺激的人气道平滑肌细胞(human airway smooth muscle cells,HASMCs)增殖和迁移的影响,及其对细胞外信号调节激酶(extracellular signal regulated kinases,ERK)信号通路的干预作用-方法:体外培养HASMCs分为6组:对照组-PDGF-BB组-sunitinib与PDGF-BB联合干预组-sunitinib组-U0126组-PDGF-BB与U0126联合干预组-流式细胞术检测HASMCs细胞周期,Transwell法观察细胞迁移,Western blot法检测ERK的磷酸化-结果:与对照组相比,PDGF-BB(20 ng/ml)显著诱导HASMCs增殖和迁移(P < 0.01),sunitinib(3 nmol/L)显著抑制PDGF-BB诱导的HASMCs的增殖和迁移,其作用与U0126相当(P > 0.05)-PDGF-BB组ERK磷酸化水平较对照组明显增高(P < 0.01)-sunitinib干预后可使PDGF-BB诱导的ERK磷酸化程度下降,其对PDGF-BB诱导的ERK磷酸化的抑制作用与ERK特异性拮抗剂U0126对PDGF-BB诱导的ERK磷酸化的抑制作用相当-结论:sunitinib抑制PDGF-BB诱导的HASMCs的增殖和迁移,可能是通过调节ERK通路起作用-

    Abstract:

    Objective:To investigate the effect of sunitinib on platelet-derived growth factor(PDGF)induced human airway smooth muscle cells(HASMCs) proliferation, migration and phosphorylation of ERK(p-ERK). Methods: HASMCs derived from human bronchus were divided into six groups: normal group, PDGF-BB group, PDGF-BB and sunitinib intervention group, sunitinib intervention group, U0126 intervention group, PDGF-BB and U0126 intervention group. Cell cycle progression was analyzed by flow cytometry. Migration was examined by Transwell test. The protein expressions of p-ERK were determined by Western blot analysis. Results: PDGF-BB (20 ng/ml) increased the proliferation and migration of HASMCs significantly (P < 0.01); sunitinib(3 nmol/L) decreased the proliferation and migration of HASMCs stimulated by PDGF-BB significantly(P < 0.05), which was no difference compared with U0126. The expression of p-ERK in PDGF-BB group was higher than that of the normal group(P < 0.01), which can be decreased by sunitinib. There is no difference between the effect of sunitinib and U0126 on p-ERK expression induced by PDGF-BB. Conclusion: Sunitinib can directly inhibit HASMCs proliferation and migration induced by PDGF-BB through the modulation of the ERK pathway.

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刘 媛,黄 茂,李 涛,刘 红. sunitinib对人气道平滑肌细胞增殖?迁移和ERK磷酸化的影响[J].南京医科大学学报(自然科学版),2011,(6):803-808

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  • 收稿日期:2010-12-13
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