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
Related in: MedlinePlus
Mentions: We next determined whether sorafenib/regorafenib interacted with sildenafil in vivo to kill tumor cells. Initial studies examined the ex vivo plating efficiency of tumor cells treated in vivo with regorafenib and sildenafil. Treatment of tumors with regorafenib and sildenafil in vivo caused a reduction in the ex vivo plating efficiency of isolated tumor cells following drug exposure; thus the long-term colony forming ability of drug treated cells was reduced beyond that achieved due to the proximal anti-tumor effects of the drugs (Fig. 9A). Based on the data in Figure 1, we next performed additional studies using pre-formed HuH7 tumors (~150 mm3); in our prior experience HuH7 cells have a significantly greater tumorigenic potential than either HEPG2 or HEP3B cells to grow in an athymic mouse. The a priori prediction for our HuH7 tumor studies would be that due to the lack of CD95 expression, the relative amount of killing may be more modest, although data from Figure 9A argues that in vivo killing by our regorafenib and sildenafil combination occurs. Transient treatment of animals with sildenafil did not significantly alter tumor growth whereas transient treatment with sorafenib caused a non-significant trend towards reduced growth (Fig. 9B). Combined treatment of animals with both drugs for 3 days caused a significant reduction/delay in HuH7 tumor re-growth.
Affiliation: Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, Virginia.