The effect and mechanisms of sunitinib on airway smooth cells proliferation and migration
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    Abstract:

    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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MIAO Li, HUANG Mao, YAO Xin, DU Qiang, LI Li-li. The effect and mechanisms of sunitinib on airway smooth cells proliferation and migration[J].,2010,(5):579-585.

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