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Background: Caner-initiating cells (CICs or cancer stem cells) have been shown both experimentally and clinically to be resistant to radiation. The mechanism underlying radioresistance remains unclear. Methods: In the present study, we screened 51 genes which are potentially important in mediating radioresistance of breast CICs. Results: The expression of AKT1 and AKT2 at protein and mRNA levels was dramatically increased among the screened genes by 8 Gy radiation treatment in MCF-7 mammosphere cells (predominantly CD24/CD44 CICs), but not in the bulk population of MCF-7 cells (predominantly CD24/CD44). Using apoptosis and clonogenic survival assays, we found pharmacological inhibition of AKT with selective inhibitors of AKT sensitized MCF-7 mammosphere cells, but not MCF-7 monolayer cells to radiation. Conclusion: The present findings suggest that treatment with AKT inhibitors prior to ionizing radiation treatment may be a potential benefit to patients with breast cancer, in particular to eradiate breast CICs. [ABSTRACT FROM AUTHOR]

Deletion of p53, most common genetic alteration, is observed in human tumors and reported to lead to improve in cell radioresistance. Heavy-ion irradiation (IR) could induce p53-/- cancer cells apoptosis. However, little is known regarding the molecular mechanism in this type of cell apoptosis. The present studies have focused on mechanisms state of signaling pathways as an activator of the cell fate decisions induced by heavy ion IR without p53. Carbon ion IR could induce up-regulation of E2F1 expression in cancer cells. This phenomenon was not observed in X-ray IR group. Up-regulation of E2F1 could cause a higher reduction in clonogenic survival, low level of cellular activity, G2/M phase arrest, promotion of apoptosis rate, up-regulation of phosphor-Rb, Bax, and cleaved-caspase 3 proteins expressions without p53. Changes of E2F1 expressions could partly alter radioresistance in cancer cells. The results were suggested that heavy ion IR could induce p53-/- cancer cells apoptosis via E2F1 signal pathway. Our study provides a scientific rationale for the clinical use of heavy ion as radiotherapy in patients with p53-deficient tumors, which are often resistant to radiotherapy. [ABSTRACT FROM AUTHOR]