ABSTRACT
Aim: To explore the effect of a synthetic naphthoquinone derivative on the proliferation of rat aortic vascular smooth muscle cells(RAVSMCs) stimulated by platelet-derived growth factor BB (PDGF-BB) and to clarify its mechanism underlying the anti-proliferative effect. Methods: The influence of the synthetic naphthoquinone derivative on cell cycle progression and main signal transduction pathway of cell cycle induced by PDGF-BB were investigated by cell proliferation assay, [3H] thymidine incorporation test, cell cycle process analysis and immunoblotting assay. Results: S phase cell percentage in the cell cycle was reduced, while G0/G1 phase cell percentage was increased by the synthetic naphthoquinone in a dose-dependent (0. 1, 0. 5, 1 μmol · L-1) manner. Moreover, DNA synthesis also decreased. The inhibitory rate of PDGF-BB-induced RAVSMCs proliferation achieved the maximum of 44. 4% after 24 h pre-treatment by the synthetic naphthoquinone derivative at the concentration of 1 μmol · L-1. The phosphorylation of extracellular regulated kinase l/2(ERKl/2), Akt, phospholipase C (PLC) γ1 and PDGF receptor β(PDGFRβ) induced by PDGF-BB was significantly decreased (P < 0. 01) by addtion of 1 μmol · L-1 synthetic naphthoquinone derivative. Conclusions: The synthetic naphthoquinone derivative exhibits anti-proliferation activity against RAVSMCs induced by PDGF-BB via blocking the transformation of G0/G1 phase cell into S-phase cell in the cell cycle. The mechanisms might be related to its down-regulatory effect on phosporalation level of ERK1/2, Akt, PLCγ1 and PDGFRβ.
