Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) has been implicated in intimal
hyperplasia,
atherosclerosis and restenosis following
percutaneous coronary intervention.
Formononetin, a
phytoestrogen extracted from the root of Astragalus membranaceus, has been widely used in Chinese tradition medicine due to its protective effects against certain symptoms of
cancer,
hypertension,
inflammation,
hypoxia-induced cytotoxicity and
ovariectomy-induced bone loss. However, the effect of
formononetin on
platelet-derived growth factor (
PDGF)-BB-induced proliferation and migration of VSMCs, as well as the underlying molecular mechanism, remains largely unclear. In the present study, treatment with
formononetin significantly inhibited
PDGF-BB-induced proliferation and migration of human VSMCs. Investigation into the underlying molecular mechanism revealed that the administration of
formononetin suppressed
PDGF-BB-stimulated switch of VSMCs to a proliferative phenotype. Furthermore, treatment with
formononetin inhibited the
PDGF-BB-induced upregulation of cell cycle-related
proteins,
matrix metalloproteinase (MMP2) and MMP9. In addition, the that administration of
formononetin inhibited the phosphorylation of AKT induced by
PDGF-BB in VSMCs. The present results suggest that
formononetin has a suppressive effect on
PDGF-BB-stimulated VSMCs proliferation and migration, which may occur partly via the inhibition of AKT signaling pathway. Therefore,
formononetin may be useful for the treatment of intimal
hyperplasia,
atherosclerosis and restenosis.