Effects of Carbon Ion Beam on Pancreatic Cancer Stem-Like Cells In Vitro and In Vivo

PurposeTo investigate whether a carbon ion beam has beneficial effects compared to X-rays by targeting putative human pancreatic cancer stem cells. MaterialsHuman pancreatic cancer stem-like cells sorted from MiaPaca2, BxPc3, PANC1 and PK45 cells were treated with or without carbon ion or X-ray irradiation and then colony formation assay, spheroid formation assay, FACS analysis, as well as tumor formation analysis were performed. ResultsThe relative biological effectiveness (RBE) values of a carbon ion beam relative to X-ray for above pancreatic cancer cells at the D10 values were 1.71-2.18. The ability for colony, spheroid formation, and tumorigenicity from cancer stem-like CD44+/CD24+ cells is significantly higher than that from non-cancer stem-like cells CD44-/CD24-cells. FACS data showed that CD44+/CD24+ cells were more highly enriched after X-rays compared to carbon ion irradiation at isoeffective doses. The RBE values for the carbon ion beam relative to X-ray at the D10 levels for CD44+/CD24+ cells were 2.0-2.19. The number of gammaH2AX foci in CD44-/CD24- cells was higher than that of CD44+/CD24+ cells after irradiation with either X-ray or carbon ion beam. The number of gammaH2AX foci in CD44+/CD24+ cells was almost the same in the early time, but it persists for significantly longer in carbon ion beam irradiated cells compared to X-rays. ConclusionCarbon ion beam has superior potential to kill pancreatic cancer stem cell-like cells, and prolonged induction of DNA damage might be one of the pivotal mechanisms of its high radiobiological effects compared to X-rays51st Annual Meeting of Particle Therapy Co-Operative Group (PTCOG51