Effects of Carbon Ion Beam Alone or in Combination with Cisplatin on Triple Negative Breast Cancer Stem-Like Cells

AimsTo investigate whether a carbon ion beam alone or in combination with cisplatin has beneficial effects compared to X-ray by targeting putative triple negative (TN) breast cancer stem cells (CSCs). Materials and MethodsHuman breast CSCs sorted from MDA MB231 cells were treated with carbon ion or X-ray irradiation alone or in combination with cisplatin, and then colony, spheroid and tumor formation assays, RT-PCR Array analysis as well as immunofluorescence γH2AX foci assay were performed.ResultsThe colony, spheroid formation as well as tumorigenicity assays confirmed that CD44+/CD24- and CD44+/ESA+ cells exactly have CSC properties compared to CD44-/CD24- and CD44-/ESA- cells. CSCs were more highly enriched after X-ray or cisplatin compared to carbon ion beam. Carbon ion beam combined with cisplatin significantly suppressed colony and spheroid formation compared to that of X-ray combined with cisplatin as well as carbon ion alone. RT-PCR Array analysis showed that expression of DNA repair, apoptosis and autophagy related genes were differently altered between carbon ion beam and X-ray irradiation alone or in combination with cisplatin, and carbon ion beam combined with cisplatin more highly induced apoptosis and autophagy compared to X-ray combined with cisplatin. Immunofluorescence assay showed that not only the number but also the size of γH2AX foci in CSCs were lager 24 h after carbon ion beam combined with cisplatin compared to that of X-ray combined with cisplatin as well as carbon ion alone. ConclusionCarbon ion beam combined with cisplatin has superior potential to kill TN breast CSCs with unrepairable severe DNA damage and enhanced apoptosis as well as autophagy.The 105th Annual Meeting of the American Association for Cancer Research (AACR