Gleditsia sinensis thorn extract inhibits the proliferation and migration of PDGF-induced vascular smooth muscle cells

Abstract

The thorns of Gleditsia sinensis have been used to prevent or treat numerous diseases. The present study aimed to investigate the molecular mechanism of the ethanol extract of Gleditsia sinensis thorns (EEGS) on platelet-derived growth factor (PDGF)‑treated vascular smooth muscle cells (VSMCs). EEGS treatment was found to inhibit DNA synthesis in PDG\F-treated VSMCs in a dose-dependent manner, without cell toxicity. These inhibitory effects were associated with G1-phase cell-cycle arrest, which was caused by the decreased expression of cyclins and cyclin-dependent kinases (CDKs) and the upregulation of p27KIP1 expression in PDGF-stimulated VSMCs. Among the pathways examined, EEGS treatment was observed to only inhibit the PDGF‑induced phosphorylation of Akt. In addition, EEGS treatment suppressed the migration and invasion of VSMCs in the presence of PDGF as determined by wound-healing and Matrigel™ invasion assays. Furthermore, zymographic and western blot analyses revealed that EEGS treatment suppressed matrix metalloproteinase (MMP)-9 expression in PDGF‑treated VSMCs, which was attributed to a reduction in the binding activities of nuclear factor κ-light-chain-enhancer of activated B cells (NF‑κB), activator protein (AP)‑1 and specificity protein (Sp)‑1. These results demonstrate that EEGS induces p27KIP1‑mediated G1-phase cell-cycle arrest, reduces Akt phosphorylation and prevents MMP‑9 expression by decreasing the binding activities of NF‑κB, AP‑1 and Sp‑1 in PDGF-treated VSMCs, thus resulting in growth inhibition and the suppression of migration and invasion. These results may suggest a novel perspective for the use of EEGS in the treatment and prevention of vascular proliferative diseases.