Abstract
In order to see whether carbon ion (C-ion) beams have a biological advantage over X-rays, studies were designed to examine the effects of C-ion beams on radiosensitivity in X-ray resistant cells. Clinically relevant X-ray resistant SAS-R cells derived from human tongue cancer SAS cells were used. The cells were exposed to X-rays or Spread-Out Bragg peak (SOBP) beam C-ions. Cell survival was measured using a modified high-density survival assay. Cell survival signaling and cell death signaling were analyzed using flow cytometry. The cells were labeled with putative cancer stem cell markers such as CD44 and CD326. SAS-R cells were 1.6 times more radioresistant than SAS cells after exposure to X-rays. Cell survival was similar in each cell line after exposure to C-ion beams. SAS-R cells displayed enhanced cell survival signaling when compared to SAS cells under normal conditions. On the other hand, the phosphorylation of AKT-related proteins decreased and polycaspase activities were enhanced when cells were irradiated with C-ion beams in both cell lines. More CD44 and CD326 positive cells were seen in SAS-R cells than in SAS cells. Moreover, the marker positive cell numbers significantly decreased after exposure to C-ion beams when compared to X-rays at iso-survival doses in SAS-R cells. C-ion beams efficiently induced cell killing in X-ray resistant cells which displayed activated cell survival signaling and contained more numerous cancer stem-like cells.
Highlights
Radiotherapy (RT) is one of the major therapeutic modalities for eradicating malignant tumors
We speculated that carbon ion (C-ion) beams may enhance apoptosis and/or autophagy, and may target cancer stem cell (CSC) via the depression of AKT survival signaling in X-ray resistant cancer cells
After exposure to X-rays, SAS-R cells were found to be 1.6 times more radioresistant than SAS cells, the cell survival rate was similar in each cell line after exposure to C-ion beams (Figure 1)
Summary
Radiotherapy (RT) is one of the major therapeutic modalities for eradicating malignant tumors. It was shown that the CRR cells acquired radioresistance through the activation of the serine/ threonine protein kinase B (PKB, known as AKT) survival signaling pathway [5] [7] [8] This pathway controls cellular “on-off switches” related to apoptosis and autophagy which are induced by radiation [10]. The CSC theory hypothesizes that tumors contain heterogeneous cell populations and that tumor growth is driven by a discrete subpopulation of CSCs which are defined by their capacity for self-renewal and by their ability to generate heterogeneous lineages of cancer cells [13] These CSCs can provide a reservoir of cells which can lead to tumor recurrence, even after RT, through the presence of efficient DNA repair machinery and a resistance to apoptosis [14]-[16]. A cell’s fate might be determined by a balance between cell survival and death after irradiation through AKT survival signaling
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