There are few safe and effective drugs available that protect healthy tissue against radiation-induced damage, highlighting the need to develop such radioprotective agents. We investigated the mechanism underlying the protective effects of the novel, recombinant, flagellin-like protein FlaA N/C against radiation-induced tissue damage in female BALB/c mice. FlaA N/C treatment increased the levels of several pro-proliferative cytokines while inhibiting apoptosis and reducing inflammation. These effects were accompanied by activation of the nuclear factor κB signaling pathway via direct interaction of FlaA N/C with Toll-like receptor 5, as well as enhanced survival of mice after total-body irradiation compared to that observed with treatment with amifostine, a radioprotective agent that is currently being used in clinical practice. These results indicate that FlaA N/C could be further explored as a possible protector of damage to healthy tissue during radiotherapy.
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-κB (NF-κB) 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-κB 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.
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