The uptake of boron into tumor cells is a key factor in the biological effects of boron neutron capture therapy (BNCT)

The uptake of boron into tumor cells is a key factor in the biological effects of boron neutron capture therapy (BNCT). cells treated with 5?M DFO, LAT1 expression was restored in HIF-1-knocked down samples in all cell lines, revealing that HIF-1 suppresses LAT1 expression in hypoxic cells. From your results of the surviving portion after BNCT combined with YC-1, treatment with YC-1 sensitized the antitumor effects of BNCT in cells cultured in hypoxia. has already been performed in many previous studies, and therefore, treating cultured cells with DFO for analysis of hypoxia TNFSF8 in this study is appropriate [15, 16]. On the other hand, the disadvantage of DFO is that the intracellular oxygen state induced by DFO is not known. Furthermore, the chelating effect of DFO and the hypoxia weight in cultured cells may produce different effects on organelles. However, evaluation of the HIF-1 protein expression level showed a similarity between pseudo-hypoxic conditions induced by DFO and hypoxic conditions induced by reduced oxygen (Fig. 4D). In addition, from your fluorescence imaging of hypoxic conditions using MAR, it was found that we could evaluate visually the intracellular oxygen state induced by DFO (Fig. 4E). Furthermore, regarding the gene expression of LAT1, which is involved in BPA uptake, a decrease in LAT1 expression was confirmed following DFO administration compared to normal oxygen conditions (Fig. 5DCF). Therefore, administration of DFO appears to create hypoxia-like ISA-2011B conditions. To clarify the relationship between HIF-1 accumulation in hypoxic cells and LAT1 expression, we evaluated the mRNA expression of HIF-1 and LAT1 after treatment with HIF-1 siRNA. In the pseudo-hypoxic condition using DFO, the gene expression of LAT1 increased in cells transfected with HIF-1 siRNA compared with the control (Fig. 6DCF). Therefore, the LAT1 expression level may recover by inhibiting HIF-1 expression. Our study showed for the first time that LAT1 expression is controlled by HIF-1, the key ISA-2011B factor in the cellular hypoxic response. Restoration of LAT1 expression in hypoxic cells may lead to increased boron uptake in cells and decreased cell survival after BNCT, resulting in improvement in therapeutic outcomes following BNCT. Introduction of siRNA is usually involved in the toxicity and the metabolism of the cell can thereby decrease, and it is suggested that BPA uptake may have been masked in both sicontrol- and siHIF-induced samples. Therefore, it was hard to show the changes in boron concentration in HIF-1-depleted cells. Finally, we evaluated the possibility of sensitization of cells to the therapeutic effects of BNCT by using a HIF inhibitor in hypoxic conditions. It was confirmed that this gene expression of LAT1 recovered under HIF-1 knockdown conditions in all cells that we evaluated. However, in the results of the surviving portion after neutron irradiation for hypoxic cells treated with BPA, a meaningful difference was not recognized between normal oxygen conditions and hypoxia in MCF-7 cells (Fig. 3). In this study, all cell lines were irradiated under the same neutron beam conditions. Therefore, it was suggested that the sensitivity of MCF-7 cells to BNCT may have been higher than that of the other cell lines depending on cell-specific relative biological effectiveness or BPA uptake. This result might have revealed that the impact of hypoxia on BPA uptake depends on the original sensitivity to BNCT. YC-1 inhibits platelet aggregation and ISA-2011B is used pharmacologically [17, 18]. The details of the mechanism of YC-1 are not obvious but YC-1 suppresses the activity of HIF-1 in malignancy cells [19], and in this study, the decrease of HIF1- protein in YC-1-treated cells was confirmed (Fig. 7C). In addition, YC-1 has a radiosensitization effect on tumors with hypoxic fractions when used.