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Sesamin Inhibits PDGF-Mediated Proliferation of Vascular Smooth Muscle Cells by Upregulating p21 and p27
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文摘
Sesamin, an active ingredient of Asiasarum heterotropoides, is known to exhibit many bioactive functions, but the effect thereof on vascular smooth muscle cell (VSMC) proliferation remains poorly understood. Hence, we explored the antiproliferative action of sesamin on VSMCs and the underlying mechanism thereof, focusing on possible effects of sesamin on cell cycle progression. Sesamin significantly inhibited platelet-derived growth factor (PDGF)-induced VSMC proliferation (inhibition percentage at 1, 5, and 10 渭M sesamin was 49.8 卤 22.0%, 74.6 卤 19.9%, and 87.8 卤 13.0%, respectively) in the absence of cytotoxicity and apoptosis, and PDGF-induced DNA synthesis; and arrested cell cycle progression in the G0/G1-to-S phase. Sesamin potently inhibited cyclin D1 and CDK4 expression, pRb phosphorylation, and expression of the proliferating cell nuclear antigen (PCNA); and upregulated p27KIP1, p21CIP1, and p53. The results thus indicate that the antiproliferative effect of sesamin on PDGF-stimulated VSMCs is attributable to arrest of the cell cycle in G0/G1 caused, in turn, by upregulation of p27KIP1, p21CIP1, and p53, and inhibition of cyclin E鈥揅DK2 and cyclin D1鈥揅DK4 expression.

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