Study on the inhibition of platelet function by fulvestrant
Objective To investigate the effect of fulvestrant on platelet function and its related mechanism.Methods Different concentrations of fulvestrant(0.1,1 and 10 µmol/L)and solvent control(0.25％dimethyl sulfoxide(DMSO))were co-incubated with human platelets in vitro,and then the effects of fulvestrant on platelet aggregation and ATP release stimulated by thrombin,collagen and U46619 were detected by aggregometer.The expression of P-selectin on the platelet surface and the activation of integrin αⅡbβ3 were detected by flow cytometry.The effect of fulvestrant on platelet spreading on the fibrinogen surface was observed by fluorescence microscopy.The phosphorylation levels of AKT Ser473 and PKC proteins were detected by western blotting.Results Fulvestrant could inhibit platelet aggregation and ATP release induced by thrombin,collagen and U46619,inhibit the expression of P-selectin,integrin αⅡbβ3 activation and platelet spreading,and reduce the phosphorylation levels of AKT Ser473 and PKC.Conclusion Fulvestrant inhibits platelet aggregation,release and spreading,and its mechanism is related to the regulation of AKT and PKC protein phosphorylation levels.It can be used as a potential antiplatelet drug.
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