Effects of Combined Action of Neutron and Proton Radiation on the Pool of Breast Cancer Stem Cells and Expression of Stemness Genes In Vitro

Radiation response of cancer stem cells was studied in two breast cancer cell lines: luminal A (MCF-7) and triple negative (MDA-MB-231) subtypes. The relative number of CD44(+)CD24(-/low) cancer stem cells of the MCF-7 line increased by 1.7 times under the influence of gamma-irradiation at a dose of 4 Gy (p=0.047 in comparison with the control). However, no significant changes were found in the relative number of cancer stem cells and the expression level of OCT4, NANOG, and SOX2 genes after neutron, proton beam irradiation or their combined action at a total equieffective dose of 4 Gy in comparison with the control in both cell lines. The absolute number of cancer stem cells decreased under the influence of neutron or proton radiation in comparison with the control (p<0.05 for both cell lines). At the same time, the effects of sequential exposures to neutron and proton radiation on the size of the cancer stem cell pool depended on the molecular subtype of cancer cells. Additive interaction was observed for MCF-7 line and antagonistic one for MDA-MB-231 line (coefficients of synergism were 0.96 and 0.45, respectively).