会議発表用資料 Eradication of Cancer Stem Cells Using Carbon Ion Beam in Combination with DNA Damaging Drugs

崔, 星

2016-11-26
内容記述
Here I try to report our recent new findings on the mechanisms of high radiocurability produced by carbon ion beam alone or in combination with DNA damaging drugs (gemcitabine, cisplatin) from the point of view of targeting pancreatic and breast CSCs in vitro and in vivo. The colony, spheroid formation as well as tumorigenicity assays confirmed that subpopulation of CD44+/ESA+, and CD44+/CD24- cells exactly have CSC properties compared to CD44-/ESA-, CD44-/CD24+ cells in pancreatic and breast cancer cells. The relative biological effectiveness (RBE) values for the carbon ion beam relative to X-ray at the D10 levels for CSCs were 2.1-2.4. 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 and breast cancer cells. Immunofluorescence assay showed that not only the number but also the size of gammaH2AX foci in CSCs were lager 24 h after carbon ion beam combined with gemcitabine or cisplatin compared to carbon ion beam and X-ray irradiation alone. Xenograft tumors from pancreatic cancer cells were not completely controlled even treated with 60 Gy of X-ray, but it was destroyed with 25 Gy of carbon ion beam combined with gemcitabine. Taken together, carbon ion beam has superior potential to kill pancreatic and breast CSCs, produced unrepairable severe DNA damage, and can achieve high curability when combined with DNA damaging drugs compared to carbon ion beam alone.
日本放射線腫瘍学会(JASTRO)第29回学術大会

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