Effect of Tumor Microenvironment on Selective Uptake of Boric Acid in HepG2 Human Hepatoma Cells.

2017 
BACKGROUND: Feasibility and efficacy of boric acid (BA)-mediated boron neutron capture therapy (BNCT) was first demonstrated by eliminating hepatocellular carcinoma (HCC) in a rat model. Furthermore, selective uptake of BA by liver tumor cells was shown in a rabbit model. To gain further insight, this study aimed to investigate the mechanisms of transportation and selective uptake of BA in HepG2 liver tumor cells. MATERIALS AND METHODS: Transportation of BA in HepG2 cells was analyzed by time-course assays and by analyzing the rate of diffusion versus the concentration of BA. The effect of different tumor conditions on BA uptake was studied by treating HepG2 cells with 25 μg 10B/ml BA under different concentrations of glucose, at different pH and in the presence of water-soluble cholesterol. RESULTS: HepG2 cells mainly uptake BA by simple diffusion. Cell membrane permeability may also contribute to tumor-specific uptake of BA. CONCLUSION: The selective uptake of BA was achieved primarily by diffusion, while other factors, such as low pH and increased membrane fluidity, which are hallmarks of HCC, might further enhance BA uptake.
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