The Radiosensitization of Sodium Glycididazole on Nasopharyngeal Carcinoma Cells via Enhancing DNA Damage and Promoting Apoptosis

Background: The radioresistance of nasopharyngeal carcinoma (NPC) was the main cause of radiotherapy failure and it was still a challenge in the treatment of advanced NPC patients. Previous clinical studies demonstrated that sodium glycididazole(CMNA) can enhance the radiosensitivity of NPC, but the corresponding cellular mechanisms or processes remains largely unclear. Methods: To clarify the radiosensitizing effects of CMNA on NPC cells and reveal its cellular mechanisms, its effect on cell survival of NPC cells was assessed by MTT and clonogenic assay, with or without radiation. The potential cellular mechanisms such as cell cycle distribution, Apoptosis and DNA damage were assessed. A retrospective analysis of the outcome of patients with III-IV stage NPC who undergo same radiochemotherapy with or without concurrent CMNA treatment was performed to elucidate the role of CMNA in the improvement of the curative effects. Results: The treatment with CMNA at the concentration lower or close to the clinical dosage had little effect on cell survival, cell cycle distribution and a weak effect on DNA damage and cell Apoptosis of NPC cells. The combination of CMNA and radiation significantly increased the DNA damage and enhanced the Apoptosis of NPC cells, but did not significantly alter the cell cycle distribution as compared with the irradiation (IR) alone. A total of 99 patients who underwent radiochemotherapy were categorized into those with (treatment group, n=52) and without (control group, n=47) the treatment with CMNA. The complete response rates of patients in treatment group were significantly higher than in control group. Conclusions: Our results suggested that CMNA enhance the sensitivity of the NPC cells to radiation via enhancing DNA damage and promoting cell Apoptosis. It provides clues for further investigation of the molecular mechanism of the radiosensitization of CMNA on NPC cells.

nasopharyngeal carcinoma; radiotherapy; sensitization; sodium glycididazole.