The Radiosensitizing Potential of Rigosertib and Dinaciclib in Ewing's Sarcoma Cells

Abstract

Ewing’s sarcoma is the second most frequent bone cancer. However, it is still a relatively uncommon cancer, with only approximately 225 new cases diagnosed in patients under 20 years old each year in North America. Despite the low incidence of Ewing’s sarcoma, it is still deadly for a large proportion of metastatic cases. In addition, treatment can induce secondary cancers due to the high radiation dosage required for definitive radiotherapy. The purpose of this research is to test the possibility of chemotherapeutic agents to increase the radiosensitivity of Ewing’s sarcoma cells, as well as to compare the effects of each treatment type based on cell size, in order to improve the effectiveness and specificity of the treatment. The two inhibitors of interest for this study, Rigosertib and Dinaciclib, demonstrated increased radiosensitization for all cell types compared to the control. Additionally, there were no significant differences in radiosensitivity between cell types, indicating that both drugs function equally well in Ewing’s sarcoma cells regardless of differences in cell size. The mechanism of action for each inhibitor was examined by protein immunoblot analysis, which showed a decrease in PLK1 protein expression after treatment with Rigosertib, but no change in CDK1 expression following treatment with Dinaciclib. These results indicate the potential of using the inhibitors Rigosertib and Dinaciclib as effective radiosensitizing agents for the treatment of Ewing’s sarcoma.