The Effect And Mechanisms Of Sunitinib On Airway Smooth Cells Proliferation And Migration

To investigate the effect and mechanisms of sunitinib malate (sunitinib ) on PDGF-BB-induced proliferation and migration in human airway smooth muscle cells (HASMCs).Methods: HASMCs derived from human bronchus were qualified in morphology in inverted microscope and immunocytochemistry, which were divided into four groups: normal group, PDGF-BB group, PDGF-BB and sunitinib intervention group, sunitinib group. The effects of PDGF-BB on the proliferation of cultured HASMCs and the intervention of sunitinib was measured by MTT. The effects of PDGF-BB and sunitinib on the Cell cycle progression were analyzed by flow cytometry. The effects of PDGF-BB on the migration of cultured HASMCs and the intervention of sunitinib were examined using Boyden chamber apparatus. The protein expressions of p-PDGFR-βand p- AKT of HASMCs were determined by Western blot analysis. Results: (1) PDGF-BB (20 ng/ml) significantly induced proliferation of HASMCs as compared to controls(P<0.05) , Sunitinib (0.3–9nmol/L) inhibited the HASMCs proliferation in dose-dependent manner in response to PDGF-BB (20 ng/ml) . (2) Flow cytometry disclosed that PDGF-BB (20 ng/ml) increased significantly S phase of HASMCs (P<0.05); Sunitinib decreased S phase of HASMCs stimulated by PDGF-BB (P<0.05). (3) PDGF-BB (20 ng/ml) caused significantly increase in migration of HASMCs as compared to controls(P<0.05) , which was blocked by sunitinib in dose-dependent manner as compared to PDGF-BB group . (4) The phosphorylated protein expression level of PDGFR-βand AKT of HASMCs in PDGF-BB group were higher than that of the normal group (P<0.05), but that decreased in PDGF-BB and sunitinib intervention group with respect to control(P<0.05).Conclusions: It appears that sunitinib can directly inhibit PDGF-BB induced HASMCs proliferation and migration through the modulation of the PI3K/ Akt pathway.