@article{oai:repo.qst.go.jp:00047508, author = {Sai, Sei and Vares, Guillaume and Ho, Kim Eun and Karasawa, Kumiko and Bing, Wang and Nenoi, Mitsuru and Horimoto, Yoshiya and al, et and 崔 星 and Guillaume Vares and Kim Eun Ho and 唐澤 久美子 and 王 冰 and 根井 充 and 堀本 義哉}, issue = {166}, journal = {Molecular Cancer (Online Only URL:http://www.molecular-cancer.com/)}, month = {Aug}, note = {Aims: Although a relatively small proportion of all breast cancer (BC), triple negative (TN) BC is responsible for a relatively large proportion of BC deaths because of its worse clinical outcome. To investigate whether a carbon ion beam alone or in combination with cisplatin has a beneficial effect compared to X-rays, we target triple negative (TN) breast cancer stem-like cells (CSCs). Methods: Human breast CSCs sorted from MDA-MB-231 cells were treated with a carbon ion beam or X-ray irradiation alone or in combination with cisplatin (CDDP), and then colony, spheroid and tumor formation assays, RT-PCR Array analysis, and immunofluorescence γH2AX foci assay were performed. Results: The colony, spheroid formation, and tumorigenicity assays confirmed that CD44+/CD24- and ESA+/CD24- cells have CSC properties in MDA-MB-231 and MDA-MB-453 cells, respectively. The proportion of CSCs was more enriched after CDDP combination with either X-ray or carbon ion beam, however carbon ion beam combined with CDDP significantly suppressed colony and spheroid formation and more significantly inhibited cell cycle progression (sub-G1 arrest) compared to X-ray combined with CDDP or carbon ion beam alone. RT-PCR Array analysis showed that carbon ion beam combined with CDDP significantly induced apoptosis-related Cytochrome c, almost completely eliminated expression of the CSC markers CD44 and ESA, and significantly inhibited angiogenesis, and metastasis-related HIF1α and CD26 compared to carbon ion beam alone, X-ray alone, or X-ray combined with CDDP. The immunofluorescence assay showed that not only the number but also the size of γH2AX foci in CSCs were larger 24 h after carbon ion beam combined with CDDP compared to those of X-ray alone and X-ray combined with CDDP. Conclusions: Carbon ion beam combined with CDDP has superior potential to kill TN breast CSCs with irreparable severe DNA damage and enhanced apoptosis.}, title = {Carbon Ion Beam Combined with Cisplatin Effectively Disrupts Triple Negative Breast Cancer Stem-Like Cells In Vitro}, volume = {14}, year = {2015} }