METHODS

In vitro assays were performed using ribavirin and radiation in a sacral chordoma cell line (U-CH1). Cellular growth was quantified over three time points using proliferation assays. Clonogenic potential was determined via colony formation assays. An animal model was established by subcutaneously implanting U-CH1 tumor into the hindlimb of athymic immunodeficient mice. Flank tumor growth was assessed at regular time intervals in animals treated with vehicle control (H2O), ribavirin (150mg/kg), radiation (3Gy), or ribavirin+ radiation.

RESULTS

Ribavirin (10μM) and radiation (2Gy) independently decreased cell growth in U-CH1 cells, and their combination led to a greater reduction compared to ribavirin (P=. 0100) or radiation (P=. 0012) alone. Ribavirin (50μM) independently decreased colony formation compared to controls (P=. 0011), and combination therapy with radiation led to a greater reduction in colony formation compared to ribavirin (P=. 0034) or radiation (2Gy: P=. 0014, 4Gy: P=. 0196) alone. In vivo, compared to vehicle-treated controls, a significant reduction in flank tumor volume was seen following the combination of ribavirin and radiation (P=. 0149), but not ribavirin or radiation alone.

CONCLUSION

Treatment of chordoma with ribavirin reduced cell growth and clonogenic potential and sensitized to radiation therapy in vitro. Combination therapy with ribavirin and radiation led to a significant reduction in flank tumor volume in a chordoma animal model. Further work is needed to characterize the potential therapeutic benefit of ribavirin as a radiosensitizing agent in chordoma.