| Objective: To study the effects of artesunate on the proliferation and apoptosis of cultured rat aortic vascular smooth muscle cells (rVSMCs) and explore the mechanism.Methods: Rat aortic VSMCs were cultured in vitro and divided randomizedly into 4 groups: the solvent control group and three drug groups(low, moderate and high concerntration) . Light microscopy was used to observe the morphology of rVSMCs. Cell counting was used to confirm the proliferation of rVSMCs. MTT assay was used to test the activation of rVSMCs. Western Blot was used to detect the expression of ERK1/2 and activation of p-Akt and caspase-9 in Ras signaling pathway.Results: (1)With the increase of concerntration and time, artesunate caused a marked dose-dependent and time-dependent proliferation inhibitory effect on rVSMCs in all the three groups. In addition to this, cell death was observed in the high-dose group.(2)Compared with the solvent group, artesunate showed significantly proliferation inhibitory effects with obvious dose and time dependency between 10μmol/L and 50μmol/L, especially in high-dose group with the nearly complete proliferation inhibition rate (P<0.01). (3)Compared with the solvent group, artesunate showed significantly activation inhibitory effects with obvious dose and time dependency between 10μmol/L and 50μmol/L, especially in high-dose group with the nearly complete activation inhibition rate (P<0.01).(4)Artesunate can downregulate the activation of ERK1/2, p-Akt and caspase-9 in a dose-dependent manner and enhance the activation of caspase-9.Conclusion: (1) Artesunate can effectively inhibit the proliferation of rVSMCs in vitro with obvious dose and time dependency.(2) The artesunate antiproliferative effect is mainly mediated by inhibiting the activation of Ras-ERK1/2.(3) Artesunate may possibly induce the apoptosis of rVSMCs by inhibing the activation of Ras-PI3K-Akt and initiating the mitochodria pathway of apoptosis.
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