Novel recombinant protein FlaA N/C increases tumor radiosensitivity via NF-kappa B signaling in murine breast cancer cells

摘要

The recombinant protein flagellin A (FlaA) N/C, derived from the flagellin protein of Legionella pneumophila, has been shown to increase the expression of cytoprotective cytokines, activate the nuclear factor-B (NF-B) signaling pathway, and increase the survival of mice following total body irradiation. Determi ning whether FlaA N/C has a sensitizing effect on tumor radiation or a direct tumoricidal effect is critical for its application as an effective radiation protection agent. The present study investigated the molecular mechanism underlying the tumor radiosensitivity of FlaA N/C. FlaA N/C was found to increase tumor apoptosis and autophagy, regulate the cell cycle and increase radiosensitivity in 4T1 tumor cells. Furthermore, FlaA N/C was found to promote radiosensitivity by activating NF-B signaling. Finally, the present study analyzed FlaA N/C-enhanced radiosensitivity in animal models, and FlaA N/C was found to significantly prolong the survival period of mice after total body radiation. This indicates that FlaA N/C might be a novel radiation sensitizer in tumor radiation therapy.