Clinically relevant concentration of anti-viral drug ribavirin selectively targets pediatric osteosarcoma and increases chemosensitivity.

Clinically relevant concentration of anti-viral drug ribavirin selectively targets pediatric osteosarcoma and increases chemosensitivity. Biochem Biophys Res Commun. 2018 Nov 30;506(3):604-610 Authors: Chen J, Xu X, Chen J Abstract Ribavirin is an anti-viral drug but has recently gained attention as a potential candidate for cancer treatment. In line with these efforts, our work is the first to demonstrate that ribavirin, at clinically relevant concentration, selectively targets pediatric osteosarcoma and increases chemosensitivity. Using preclinical osteosarcoma cell and xenograft models, we found that ribavirin is active against osteosarcoma bulk and subpopulations with highly proliferative and invasive properties via inhibiting growth, inducing apoptosis and suppressing colony formation. At the same concentrations, ribavirin either did not or affected human normal osteoblastic cell and fibroblast cells in a less extent than osteosarcoma cells. Notably, the combination of ribavirin with doxorubicin resulted in greater efficacy than single drug alone. The combination completely arrested the osteosarcoma growth in vivo throughout the whole duration of drug treatment. We further showed that ribavirin acted on osteosarcoma largely via targeting eIF4E. In addition to eIF4E, ribavirin also modulated phosphorylation of Erk and expression of EZH2 and Snail without affecting Akt and mTOR. Lastly, we found that eIF4E expression and phosphor...
Source: Biochemical and Biophysical Research communications - Category: Biochemistry Authors: Tags: Biochem Biophys Res Commun Source Type: research