JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES) ›› 2014, Vol. 52 ›› Issue (12): 35-40.doi: 10.6040/j.issn.1671-7554.0.2014.575

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Effect and mechanism of isorhynchophylline on platelet-derived growth factor(PDGF)-BB-induced pulmonary artery smooth muscle cell proliferation

ZHANG Xin, GUO Haipeng, WANG Zhenhong, TANG Linna, YANG Jie, WU Dawei   

  1. Department of Critical Care Medicine, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China
  • Received:2014-09-04 Revised:2014-11-06 Published:2014-12-10

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Abstract: Objective To investigate the effect of isorhynchophylline on platelet-derived growth factor (PDGF)-BB-induced pulmonary artery smooth muscle cells (PASMCs) proliferation and the related mechanism. Methods In PDGF-BB-induced PASMCs proliferation model, the effect and cytotoxicity of isorhynchophylline on PDGF-BB-induced PASMCs proliferation were measured by MTT assay and trypan blue exclusion, and the cell cycle progression was measured by flowcytometry. The expression of cell cycle-related protein and PDGF receptor β (PDGF-Rβ) signaling pathway in PDGF-BB-stimulated PASMCs were measured by Western blotting. Results Compared with the controls, the number of PASMCs increased approximately 2.5 fold after cultured with 20 ng/mL PDGF-BB for 24 h. Isorhynchophylline inhibited PDGF-BB-induced PASMCs proliferation in a concentration-dependent manner. 25 μmol/L isorhynchophylline inhibited the increase of PDGF-BB-induced PASMCs S phase proportion. Western blotting results indicated that isorhynchophylline decreased PDGF-BB-induced expressions of cyclin D1 and CDK6, and inhibited p27kip1 degradation. Furthermore, isorhynchophylline negatively regulated PDGF-BB-induced phosphorylation of PDGF-Rβ and its downstream signaling molecules, including AKT and glycogen synthase kinase (GSK) 3β. Conclusion Isorhynchophyl-line inhibited PDGF-BB-induced PASMCs proliferation via inducing G0/G1 phase arrest, the possible mechanism of which is that isorhynchophylline modulate synthesization and degradation of cell cycle-related protein by inhibiting PDGF-Rβ and its downstream signaling pathway.

Key words: Isorhynchophylline, Pulmonary artery smooth muscle cell, Proliferation, Glycogen synthase kinase 3β, Platelet-derived growth factor

CLC Number: 

  • R543.2
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