Koji Harada1, Tarannum Ferdous2, Yoshiya Ueyama2. 1. Department of Oral and Maxillofacial Surgery Yamaguchi University Graduate School of Medicine, Ube, Japan harako@yamaguchi-u.ac.jp. 2. Department of Oral and Maxillofacial Surgery Yamaguchi University Graduate School of Medicine, Ube, Japan.
Abstract
BACKGROUND/AIM: Gimeracil or 5-chloro-2, 4-dihydroxypyridine (CDHP) has been reported to exert radiosensitization effects in cancer cells by suppressing DNA repair pathways. Here, we investigated the antitumor effect of gimeracil and radiation combination therapy against oral squamous cell carcinoma (OSCC). MATERIAL AND METHODS: The antitumor activity of gimeracil and/or radiation was investigated in HSC2 and/or SAS cells by growth inhibition assays and clonogenic survival assay. The expression of DNA double-strand break repair proteins were assessed by western blotting and immunohistochemistry, also fluorescent measurements of intracellular reactive oxygen/nitrogen species (ROS/RNS) were carried out in gimeracil and/or radiation-treated HSC2 cells/tumors. RESULTS: Gimeracil and radiation combination treatment significantly inhibited OSCC cell/tumor growth and colony formation. Down-regulated expressions of DNA double-strand break repair proteins were observed in gimeracil and/or radiation treated cells/tumors. Additionally, the growth inhibitory effect of this combination treatment was associated with reactive oxygen species/reactive nitrogen species (ROS/RNS) generation. CONCLUSION: Gimeracil might exert radiosensitizing effects on OSCC cells. Copyright
BACKGROUND/AIM: Gimeracil or 5-chloro-2, 4-dihydroxypyridine (CDHP) has been reported to exert radiosensitization effects in cancer cells by suppressing DNA repair pathways. Here, we investigated the antitumor effect of gimeracil and radiation combination therapy against oral squamous cell carcinoma (OSCC). MATERIAL AND METHODS: The antitumor activity of gimeracil and/or radiation was investigated in HSC2 and/or SAS cells by growth inhibition assays and clonogenic survival assay. The expression of DNA double-strand break repair proteins were assessed by western blotting and immunohistochemistry, also fluorescent measurements of intracellular reactive oxygen/nitrogen species (ROS/RNS) were carried out in gimeracil and/or radiation-treated HSC2 cells/tumors. RESULTS:Gimeracil and radiation combination treatment significantly inhibited OSCC cell/tumor growth and colony formation. Down-regulated expressions of DNA double-strand break repair proteins were observed in gimeracil and/or radiation treated cells/tumors. Additionally, the growth inhibitory effect of this combination treatment was associated with reactive oxygen species/reactive nitrogen species (ROS/RNS) generation. CONCLUSION:Gimeracil might exert radiosensitizing effects on OSCC cells. Copyright