Increasing the intracellular concentration of arsenic trioxide restores the sensitivity of arsenic trioxide-resistant K562 cells to arsenic trioxide

Objective To explore the relationship between intracellular concentration of arsenic trioxide (ATO) in ATO-resistant K562 cells (K562/AS2) and ATO resistance level.Methods The K562/AS2 cells were established by gradually increasing the concentration of ATO from the parental cell line,K562.Arsenic concentration was measured with atomic fluorescence photometry.Cell viability was assessed using MTT assay.Results At exposure to 1 μg/ml ATO for 24 h,48 h and 72 h,the arsenic concentration in the K562/S cells were all significantly higher than that in the K562/AS2 cells,(15.63± 0.42) μg/L vs 0 μg/L,(22.27±0.15) μg/L vs (3.51±0.12) μg/L and (24.31±0.21) μg/L vs (3.61±0.11) μg/L (P ＜ 0.05).With increasing concentration and the extension of incubation time,concentration of arsenic in cells was gradually increased (P ＜ 0.05),which increase quickly between 1 μg/ml and 2 μg/ml.The growth inhibition rate of K562/AS2 cells was also gradually increased (P ＜ 0.05),which increased quickly between 1 μg/ml and 2 μg/ml.Linear correlation analysis showed that when the K562/AS2 cells was exposed to ATO for 24 h,48 h and 72 h,respectively,the cell growth inhibition rates were positively correlated with the intracellular concentration of ATO.Conclusions Either increasing concentrations of ATO or prolonging the exposure time to ATO can increase intracellular concentration of ATO in ATO-resistant cells,and intracellular arsenic concentration is positively related to the cytotoxicity of ATO to K562/AS2 cells.Therefore,the sensitivity to ATO of ATOresistant K562 cells could be restored by increasing the intracellular concentration of ATO. Key words: K562 cells;  Arsenic trioxide;  Drug resistance, neoplasm