Carbon Ion Beam Combined With Chemotherapy Destroys Pancreatic Cancer Stem Cells

In this study we examined carbon ion beam alone or in combination with chemotherapy (TS-1 or 5FU, or gemcitabine) on putative pancreatic cancer stem cell (CSC) in vitro and in vivo. We found that the number of colony and spheroid formed from CSCs (CD44+/ESA+) after carbon ion beam was significantly reduced compared to that of X-ray, and it was extremely suppressed when combined with gemcitabine or 5-FU. The relative biological effectiveness (RBE) values for the carbon ion beam relative to X-ray at the D10 levels for CSCs were 2.23-2.66. Not only the number but also the size of gammaH2AX foci in CSCs were lager 24 h after carbon ion beam combined with 5-FU or gemcitabine compared to carbon ion beam alone or X-ray combined with 5-FU or gemcitabine. In vivo xenograft tumor control analysis showed that the tumors were not completely controlled even treated with 60 Gy of X-ray, but it was effectively destroyed with 25 Gy of carbon ion beam combined with 50 mg/kg gemcitabine or 10mg/kg TS-1. In conclusion, carbon ion beam combined with gemcitabine or TS-1 (or 5-FU) has superior potential to kill pancreatic CSCs via unrepairable clustered DSB, and multiple cell death pathways.第47回日本膵臓学会大会(JPS),第20回国際膵臓学会(IAP),第6回アジアオセアニア膵臓学会(AOPA)合同学