Different effects of carbon ion beams and X-rays on clonogenic survival and DNA repair in human pancreatic cancer stem-like cells.

Abstract

The effects of a carbon ion beam and X-rays on human pancreatic cancer stem-like cells were examined from the point of view of clonogenic survival and DNA repair. Human pancreatic cancer stem-like cells were treated with and without carbon ion and X-ray irradiation, and then colony, spheroid and tumor formation assays as well as γH2AX foci formation assay were performed. The relative biological effectiveness (RBE) values of a carbon ion beam relative to X-ray for the MIA PaCa-2 and BxPc-3 cells at the D10 values were 1.85-2.10. 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 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 γH2AX 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 γH2AX foci in CD44(+)/CD24(+) cells was almost the same in the early time, but it persists significantly longer in carbon ion beam irradiated cells compared to X-rays. Carbon 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-rays.