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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,Westernblot检测PDGFR-β和AKT的磷酸化。结果:与对照组相比,PDGF-BB(20ng/ml)显著诱导HASMCs的增殖和迁移(P<0.05),sunitinib(0.3～9.0nmol/L)呈浓度依赖性抑制PDGF-BB诱导的HASMCs增殖和迁移;PDGF-BB(20ng/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。
Objective: To investigate the effects of sunitinib malate on the proliferation and migration of human airway smooth muscle cells (HASMCs) stimulated by platelet-derived growth factor BB (PDGF-BB) and its mechanism. Methods: HASMCs were divided into four groups: control group, PDGF-BB group, PDGF-BB and sunitinib group, sunitinib group and MTT colorimetric assay. Flow cytometry HASMCs cell cycle, modified Boyden microporous membrane dual-channel method to observe cell migration, Western blot detection of PDGFR-β and AKT phosphorylation. Results: PDGF-BB significantly induced the proliferation and migration of HASMCs compared with the control group (P <0.05). Sunitinib (0.3-9.0 nmol / L) inhibited the proliferation of HASMCs induced by PDGF-BB in a concentration- (P <0.05). The proportion of S phase in PDGF-BB and sunitinib groups was lower than that in PDGF-BB group (P <0.05) (P <0.05). The phosphorylation of PDGFR-β and AKT in PDGF-BB group was higher than that in control group (P <0.05). The PDGF-BB and sunitinib group had lower expression of PDGFR-β and AKT than PDGF-BB group. CONCLUSIONS: Sunitinib inhibits the proliferation and migration of HASMCs induced by PDGF-BB, probably by regulating the PI3K / AKT pathway.