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: We then examined the activities of multiple signal transduction pathways/proteins in tumors 7 days after the start of treatment. Treatment of HuH7 and HT29 tumors with (regorafenib + sildenafil) reduced plasma levels of FGF and GM-CSF and increased the levels of PDGFbb (Figs. 10A and 11A). Regorafenib and sildenafil treatment also reduced the expression of multiple tumor growth factors in the blood of animals carrying HuH7 tumors (Fig. 11B). In both HuH7 and HT29 tumors, we observed drug combination exposure caused activation of AKT though total S6 phosphorylation was reduced in both tumor types (Fig. 11C). These findings were associated with reduced PDGFRβ phosphorylation and decreased NFκB activity (Fig. 11D and E). As observed for HT29 tumors, obvious biomarkers for third drug combinations include AKT inhibitors, FGFR inhibitors, and ERBB1/2 inhibitors. Inhibition of AKT or ERBB1/2 signaling enhanced (regorafenib + sildenafil) killing (Fig. 11F).
Affiliation: Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, Virginia.