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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(hu-man 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、suni-tinib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,Westernblot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(3nmol/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。
OBJECTIVE: To investigate the effect of sunitinib on the proliferation and migration of human airway smooth muscle cells (HASMCs) stimulated by platelet-derived growth factor (PDGF) -BB and its effect on extracellular signal Regulate the kinase (extracellular signal regulated kinases, ERK) signaling pathway intervention. Methods: HASMCs were divided into 6 groups: control group, PDGF-BB group, sunitinib and PDGF-BB combined intervention group, suni-tinib group, U0126 group, PDGF-BB and U0126 intervention group. The cell cycle of HASMCs was detected by flow cytometry. The cell migration was observed by Transwell method. The phosphorylation of ERK was detected by Western blot. Results: PDGF-BB significantly induced the proliferation and migration of HASMCs compared with the control group (P <0.01). Sunitinib (3 nmol / L) significantly inhibited the proliferation and migration of HASMCs induced by PDGF-BB Comparable to U0126 (P> 0.05). ERK phosphorylation in PDGF-BB group was significantly higher than that in control group (P <0.01). The inhibitory effect of PDGF-BB on ERK phosphorylation induced by PDGF-BB was similar to that of ERK-specific antagonist U0126 on PDGF-BB-induced ERK phosphorylation. CONCLUSIONS: Sunitinib inhibits the proliferation and migration of HASMCs induced by PDGF-BB, probably by regulating the ERK pathway.