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Preclinical study on hypoxic radiosensitizing effects of glycididazole in comparison with those of doranidazole in vitro and in vivo

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Title: Preclinical study on hypoxic radiosensitizing effects of glycididazole in comparison with those of doranidazole in vitro and in vivo
Authors: Yasui, Hironobu Browse this author →KAKEN DB
Kubota, Nobuo Browse this author
Nishizumi, Junko Browse this author
Sakai, Yuri Browse this author
Yamamori, Tohru Browse this author →KAKEN DB
Inanami, Osamu Browse this author →KAKEN DB
Keywords: hypoxia
radiosensitizer
glycididazole
doranidazole
tumor
Issue Date: 20-Nov-2017
Publisher: Spandidos Publications
Journal Title: Oncology Letters
Volume: 15
Start Page: 1993
End Page: 1998
Publisher DOI: 10.3892/ol.2017.7481
Abstract: To overcome the radioresistance of hypoxic cells in solid tumor, numerous types of radiosensitizers specifically against them have been developed. Glycididazole has a chemical structure in which two metronidazole forms are combined, and is widely used as a hypoxic radiosensitizer in China. However, a detailed investigation of its radiosensitizing properties has not been performed. The present study reported a comparative assessment of glycididazole and doranidazole, another hypoxic radiosensitizer. All experiments were performed using the murine squamous cell carcinoma cell line SCCVII. Prior to X‑irradiation, the cells were treated with the test drugs at concentrations of 10 mM and 200 mg/kg in vitro and in vivo, respectively. Uptake and their intratumor chemical forms were analyzed by high performance liquid chromatography (HPLC). Both drugs enhanced the reproductive cell death induced by X‑irradiation under hypoxia. However, the growth delay assay of the transplanted tumor revealed the combination of X‑irradiation and glycididazole showed a similar antitumor effect to that of X‑irradiation alone, whereas doranidazole significantly sensitized the cells to X‑irradiation. HPLC analysis revealed that incorporated glycididazole was decomposed to metronidazole and was therefore present at a lower concentration compared with that of doranidazole. The decomposition of glycididazole to metronidazole reduced its radiosensitizing efficiency in vivo. Elucidation of the kinetics of drugs containing metabolizable chemical forms is necessary for the optimization of clinical treatment.
Type: article
URI: http://hdl.handle.net/2115/70456
Appears in Collections:獣医学院・獣医学研究院 (Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 稲波 修

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