International Journal of Radiation Research

en Complementary killing effect of tirapazamine in combination with radiation therapy on cells with high aldehyde dehydrogenase activity in SAS cell line Radiation Biology Radiation Biology تحقيق بديع Original Research <div style="text-align: justify;">Background: Tumor cells with high aldehyde dehydrogenase activity (ALDHhigh cells) are induced by an intratumoral hypoxic condition and lead to radioresistance, tumor recurrence, and metastasis. Therefore, to enhance the anti-tumor effect of radiotherapy, it is reasonable to efficiently control ALDHhigh cells by targeting them. In this study, we evaluated the effect of tirapazamine, a hypoxic toxin, combined with irradiation on ALDHhigh cells. Materials and Methods: Human tongue squamous cell carcinoma SAS cells were used in this study. Spheroids were irradiated with 6 Gy following treatment with 40 μM tirapazamine. After 24, 48, and 72 hours, the populations of ALDHhigh cells were analyzed. The frozen sections of spheroids were prepared, and hypoxia-inducible factor-1α-positive areas and ALDH1-positive areas were detected. Results: Compared with the cells grown in monolayer culture, the SAS cells grown in spheroids exhibited radioresistance. Furthermore, the proportion of ALDHhigh cells was significantly higher in spheroids than in monolayer culture. The ALDHhigh cells were sustained in a hypoxic fraction localized at the center of the spheroids after irradiation. Tirapazamine effectively reduced these ALDHhigh cells. The combination of tirapazamine with irradiation showed an additive cytotoxic effect in spheroids, but not in parental cells, which was consistent with a preferential killing effect of tirapazamine on ALDHhigh cells. Conclusion: Combined tirapazamine and radiotherapy administration appeared to be a reasonable approach to control ALDHhigh cells in hypoxic regions that may be involved in recurrence and metastasis. </div>     Hypoxic cytotoxin, tirapazamine, radiation-resistance, aldehyde dehydrogenase. 269 276 http://ijrr.com/browse.php?a_code=A-10-1-904&slc_lang=en&sid=1 K. Ichise 7900319475328460021810 7900319475328460021810 No Department of Radiation Oncology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori, 036-8562 Japan K. Hirose khirose@hirosaki-u.ac.jp 7900319475328460021811 7900319475328460021811 Yes Department of Radiation Oncology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori, 036-8562 Japan M. Sato 7900319475328460021812 7900319475328460021812 No Department of Radiation Oncology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori, 036-8562 Japan F. Komai 7900319475328460021813 7900319475328460021813 No Division of Radiology, Hirosaki University Hospital, 53 Hon-cho, Hirosaki, Aomori, 036-8563, Japan M. Tanaka 7900319475328460021814 7900319475328460021814 No Department of Radiation Oncology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori, 036-8562 Japan I. Fujioka 7900319475328460021815 7900319475328460021815 No Department of Radiation Oncology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori, 036-8562 Japan H. Kawaguchi 7900319475328460021816 7900319475328460021816 No Department of Radiation Oncology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori, 036-8562 Japan Y. Hatayama 7900319475328460021817 7900319475328460021817 No Department of Radiation Oncology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori, 036-8562 Japan Y. Takai 7900319475328460021818 7900319475328460021818 No Department of Radiation Oncology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori, 036-8562 Japan M. Aoki 7900319475328460021819 7900319475328460021819 No Department of Radiation Oncology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori, 036-8562 Japan