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: In prior studies, we have shown that sorafenib as a single agent can modestly promote increased numbers of autophagosomes (Park et al., 2008, 2010a,b; Martin et al., 2009; Cruickshanks et al., 2013). Treatment of cells with sildenafil and sorafenib increased the numbers of autophagosomes and autolysosomes in a greater than additive fashion (Fig. 5A and B). The increase in the numbers of autophagosomes and autolysosomes was suppressed by incubation of cells with either L-NAME or NAC. Knock down of either ULK-1, Beclin1, or ATG5 expression inhibited the drug-induced increase in autophagosome and autolysosome levels and reduced cell killing by sildenafil and sorafenib or by sildenafil and regorafenib treatments (Fig. 5C and D).
Affiliation: Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, Virginia.