Study On The Radiotherapy Sensitization Effect And Mechanism Of Deferoxamine

Radiation therapy is one of the three major measures of cancer treatment.Radiotherapy of malignant tumors often encounter radioresistance,inflammation of the skin and other troubles.The radiosensitizer can effectively inhibit the growth of tumor cells and protect the normal tissues.At present,the radiosensitizers used in clinic have the defects of drug toxicity,low specificity and lack of enough clinical trials.Therefore,it is necessary to find a more ideal radiosensitizer.Rapid dividing tumor cells require large amounts of iron compared to normal cells,and tumor cells are very sensitive to iron depletion.Studys found that iron chelator desferrioxamine can induce G1/S phase arrest,inhibit DNA synthesis and lead to apoptosis of cancer cells.In this paper,iron was treated as a target of tumor radiotherapy and we study the radiosensitizing effect of deferoxamine on human glioma U251 cells.In this study,the clonogenic assay was used to detect the radiosensitizing effect of deferoxamine on U251 cells.The cell viability and proliferation inhibition of U251 cells treated with X-ray and deferoxamine were observed at different time points by CCK-8 assay and invert fluorescent microscope.The autophagy,apoptosis,cell cycle,reactive oxygen species and cytoplasmic Ca²⁺levels were detected by flow cytometry to study the mechanism of radiosensitization of DFO.Caspase 3 Activity was detected by elisa assay.Our results showed that 50,100μmol/L of deferoxamine exhibited no significant radiosensitizing effect on U251 cells in the first day.The increasing protective autophagy of U251 cells occurs 1 day after DFO’s radiosensitization,which well explains no significant change in viability of U251 cells in the first day after the co-treatment.The radiosensitizing effect of DFO was mainly attributed to increase of apoptosis and the decrease of the level of protective autophagy on the 4th day after the co-treatment.The increased apoptosis of U251 cells four days after being treated with DFO plus X-rays is attributed to elevated levels of cytosolic calcium.This paper studied the radiosensitization effect of deferoxamine and explored the mechanism of deferoxamine’s radiosensitization,which provided a theoretical basis for the clinical application of deferoxamine as a radiosensitizer.