Correlation of hypoxia status with radiosensitizing effects of sodium glycididazole: A preclinical study

The correlation of pretreatment hypoxia status with the radiosensitization effect of sodium glycididazole (CMNa) was not previously defined. The purpose of the present study was to evaluate the tumor hypoxia status in various cancer xenografts and to investigate the correlation between tumor hypoxia status and radiosensitizing effects of CMNa based on the pharmacokinetic and pharmacodynamic parameters. Human esophageal cancer (EC109), head and neck cancer (FaDu) and lung cancer (A549) nude mice xenografts were used. The concentrations of CMNa and its metabolites in the tumors and normal tissues were determined by high-performance liquid chromatography following intravenous injection of 171.9, 57.3 or 19.1 mg/kg CMNa. The tumors were irradiated with 30 Gy in 6 fractions with CMNa administration prior to each irradiation. The tumor growth delay values were calculated for each treatment group and compared with groups treated with radiation alone. Tumor hypoxia status was verified by immunohistostaining of tissues for hypoxia inducible factor 1α (HIF-1α) staining, and the concentration of plasma osteopontin (OPN) was determined using ELISA. The correlation between OPN concentration and tumor growth delay was subsequently analyzed. It was observed that the drug concentration in the tumor was 1.6-2.8 times higher compared with adjacent muscle, particularly at high and medium doses. CMNa was able to sensitize tumors to irradiation, particularly for EC109 and FaDu xenografts at high dose (P<0.05). Furthermore, there was markedly increased expression of HIF-1α and plasma OPN levels in FaDu and EC109 xenografts compared with A549. Additionally, it was indicated that pretreatment hypoxia status might be correlated with the radiosensitizing effects of CMNa. The present data demonstrated that tumor hypoxia status might be correlated with the radiosensitizing effects of CMNa in different tumor models.