The Effect Of Ginsenoside On Anticoagulant And Anti-tumor Of Warfarin

Objective:Warfarin and ginseng have been widely used in the treatment of cardiovascular diseases.Recently,it was found that warfarin and ginseng also have anti-tumor activities.Therefore,the patients may be taken the two drugs at the same time to improve the efficacies.However,the clinical safety and effectiveness of combination use of the two drugs are still controversial,and the anti-tumor metastasis mechanism of combination use of the the two drugs are not clear yet.In the present study,we established a hyperlipemia rat model and human pulmonary microvascular endothelial cells(HPMEC)model to investigate the interactions between the warfarin and ginsenosides/Rb1.We also investigated the potential antitumor activity of combination use of warfarin and ginsenosides.Methods:A high-fat rat model was established by feeding the high-fat diet to the rats.Then,the anticoagulation effects of warfarin were detected by PT/INR and ELISA kit,after high-fat rats were co-administrated with ginsenosides and warfarin.Western Blotting analyzed the expressions of intercellular adhesion molecule ICAM-1 and vascular cell adhesion molecule VCAM-1,after the HPMEC cells were induced by the TNF-a.The anti-metastatic effect of combination uses of warfarin ginsenosides in vitro were investigated via MTT,matrix adhesion,platelet adhesion and scratching assays.Finally,we investigated the anti-metastatic mechanism of combination use of warfarin and Rb1 by Western Blotting and qRT-PCR.Results:Ginsenosides could decrese anticoagulation effects of warfarin in the high-fat rats in vivo depended in a dose-and time manner.The effect was accompanied by modulating the concentrations of coagulation factor II,VII,protein Z in the plasma,increasing the expression of liver cytochrome P450.In addition,it was showed that combine use of warfarin and Rbl could not down-regulate the levels of ICAM-1 and VCAM-1 in the HPMEC cells.On the one hand,we found that warfarin combined with Rb1 could effectively inhibit the proliferation,adhesion and migration abilities of non-small cell lung cancer A549 cells.On the other hand,the Western Blotting results showed that combine use of warfarin and Rbl could down-regulate the expressions of VCAM-1,ICAM-1,EGFR/STAT MMP-2,MMP-9 and VEGF proteins.Conclusion:There was the antagonism effect when combination use of ginsenosides and warfarin in the hyperlipemia rat model and human pulmonary microvascular endothelial cells(HPMEC)model,while there was the synergistic effect when combination use of Rb1 and warfarin in the A549 cells metastasis.