Effects of carbon ion and X-ray irradiation on pancreatic cancer stem cells

Purpose:To investigate whether a carbon ion beam has beneficial effects compared to X-rays by targeting putative human pancreatic cancer stem cells. Materials:Human pancreatic cancer stem-like cells sorted from 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 xenograft tumor growth control analyses were performed. Results:The in vitro relative biological effectiveness (RBE) values of carbon ion beams relative to X-rays calculated by the D10 levels were 1.71 to 2.18. FACS analysis showed that the proportion of cancer stem-like marker CD44+ and ESA+ cells were 4.8% and 0.9%, but CD133+ was undetectable. The proportion of CD44+, ESA+ cells was more significantly enriched by X-rays or gemcitabine treatment compared to carbon-ion irradiation. The proportion of CD44+ cells did not change after treatment with PI3K inhibitor LY29402 or MAPK inhibitor PD98059 only, but remarkably enriched in combination with X-rays or C-ion irradiation, suggesting that PI3K-AKt survival pathway as well as MAPK kinase pathway are involved in IR induced enrichment of CSC. CD44+/CD24+ and CD44+/ESA+ cells significantly have higher number of colony and spheroid compared to CD44-/CD24- and CD44-/ESA- cells. CD44+/CD24+ and CD44+/ESA+ cells showed radioresistance to both X-ray and carbon ion irradiation, but carbon ion irradiation was more effective at killing those of cancer stem-like cells. CD44+/CD24+ and CD44+/ESA+ cells have shown more potential to form tumors in SCID mice than CD44-/CD24- and CD44-/ESA- cells, and carbon ion beam more effectively eradicates xenograft tumors compared to X-rays at doses of same biological efficacy. Conclusion:Carbon ion irradiation has potential advantages over X-rays in targeting radioresistant pancreatic cancer stem-like cells.The 4th Asian-Oceanic Pancreatic Association (AOPA