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 next determined the relative expression of PDE5 and PDGFRα/β in normal liver and in hepatoma, as well as on- and off-target effects of our drugs in promoting drug combination killing. PDE5 was over-expressed in hepatocellular carcinoma tissues but not in normal liver from the same patient (Fig. 2A; similar data were obtained in multiple other samples, Fig. 2B). Knock down of PDE5 expression enhanced regorafenib toxicity in CD95 HuH7 cells (Fig. 2C). In prior studies, we have shown that PDGFRα/β play an important role in the biology of sorafenib in terms of its toxic combination with other therapeutic agents such as histone deacetylase inhibitors (Martin et al., 2009; Park et al., 2010; Cruickshanks et al., 2013). PDGFRα/β was over-expressed in hepatocellular carcinoma tissues but not in normal liver tissue from the same patient (Fig. 2D). Knock down of PDGFRα/β expression enhanced the toxicity sildenafil in tumor cells (Fig. 2E).
Affiliation: Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, Virginia.