会議発表用資料 Cutting-Edge Research in Basic and Translational Heavy-Ion Radiobiology: Focused on Radioresistant Cancer Stem Cells

崔, 星  ,  Ho Kim, Eun  ,  鈴木, 雅雄  ,  Keum, WoongSeop  ,  新田, 祐樹  ,  鈴木, 基史  ,  yoon Park, Woo  ,  藤森, 亮

2018-06-22
内容記述
Purpose We have treated more than 11000 patients with various types of cancer using carbon-ion radiotherapy and obtained encouraging results. Here we report our recent novel findings about the molecular mechanisms of high radiocurability produced by carbon ion beams alone or in combination with DNA damaging drugs or with micro RNA 200c mimic from the point of view of targeting cancer stem cells (CSCs) in vitro and/or in vivo. Methods Human pancreatic, breast and mesothelioma CSCs sorted from each cell line were treated with carbon ion beam, X-ray irradiation alone or in combination with gemcitabine, or cisplatin or miRNA200c mimic, and then cell viability assay, colony, spheroid formation ability assay, and real time PCR analysis, and xenograft tumor control analysis were performed.Results The relative biological effectiveness (RBE) values for the carbon ion beams relative to X-rays at the D10 levels for CSCs were 2.1-2.4. The colony and spheroid formation capability of CSCs was significantly inhibited by carbon ion beam combined with DNA damaging drugs or with micro RNA 200c mimic. RT Profiler PCR Array analysis showed that apoptosis- and autophagy-related gene expression was significantly induced after carbon ion beam combined with gemcitabine or cisplatin compared to carbon ion alone or X-ray combined with gemcitabine or cisplatin in pancreatic, breast cancer and mesothelioma cells. Xenograft tumors from pancreatic, breast cancer and mesothelioma cells were effectively disrupted by 25 Gy of carbon ion beam combined with 50 mg/kg gemcitabine for pancreatic xenograft tumors or 15 Gy of carbon ion beam combined with 5 mg/kg cisplatin for breast and mesothelioma xenograft tumors. Conclusions Taken together, carbon ion beam has superior potential to kill pancreatic, breast and mesothelioma CSCs, and can achieve high curability when combined with DNA damaging drugs or with microRNA 200 mimic compared to carbon ion beam alone.
44th Annual Meeting of Korean Cancer Association and the 4th International Cancer Conference

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