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Preclinical study on hypoxic radiosensitizing effects of glycididazole in comparison with those of doranidazole in vitro and in vivo
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)
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Submitter: 稲波 修
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