Nexavar/Stivarga and viagra interact to kill tumor cells.
Bottom Line: PDE5 and PDGFRα/β were over-expressed in liver tumors compared to normal liver tissue.Knock down of PDE5 or of PDGFRα/β recapitulated the effects of the individual drugs.The drug combination also reduced mTOR protein expression.
Affiliation: Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, Virginia.Show MeSH
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Mentions: Based on our unexpected findings in Figure 9, we determined using a Bio-Rad MAGPIX multiplex system the expression levels of human cytokines in mouse plasma and the expression and activity of signal transduction proteins within the established tumor itself. Regorafenib and sildenafil exposure for 7 days decreased the plasma levels of bFGF and GM-CSF but significantly increased the expression of PDGFbb (Fig. 10A). In agreement with data in Figure 8, treatment of tumors for 7 days with FTY720 increased plasma levels of FAS-L (Fig. 10B). For a number of cytokines, e.g., endoglin, IL6, VEGF-A/C/D, endpoietin 2, EGF, their plasma level declined in vehicle control treated tumors over 7 days of growth which was associated with a mean of approximately sevenfold increase in tumor volume (Fig. 10B–F). In this respect, treatment of tumors with FTY720 or with regorafenib and FTY720 prevented the decline in plasma cytokine levels that were observed in mice with vehicle control treated tumors at day 7 (Fig. 10B–G). For tumors exposed to regorafenib and sildenafil, the expression of pro-growth/pro-angiogenic/pro-invasion cytokines was either unchanged compared to vehicle control treated tumors or was significantly reduced (Fig. 10C–G).
Affiliation: Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, Virginia.