Doranidazole in the radiosensitization of hypoxic pancreatic cancer cells

Objective: To investigate the effects of a new radiosensitizer, nitroimidazole-derivative--Doranidazole on pancreatic cancer cells under hypoxic condition. Methods: The human pancreatic cancer cell lines were exposed in vitro to a single fraction of high dose γ-ray radiation either with doranidazole or under hypoxic condition. The percentage of dead cells was analyzed with a multi well plated reader and the fluorescence intensities of propidium iodide before and after a digitonin treatment were measured. The sensitizing effect of doranidazole on cell killing by high-dose irradiation was evaluated by time-course, dose-dependency, and microscopic observations. The selective radiosensitive effect of doranidazole on hypoxic cells was evaluated by flow cytometry. Results: Of seven pancreatic cancer cell lines , the mortalities of 5 cell lines were significantly increased in presence of doranidazole under hypoxic condition 5 days after 30 Gy irradiation, but not under aerobic condition. Meanwhile, the radiosensitizing effect of Doranidazole on pancreatic cancer cells was demonstrated as time- and dose-dependent manner. Conclusion: Doranidazole can enhance the radiosensitivity on pancreatic cancer cells under hypoxic condition with high-dose irradiation. (authors)