| MDR is one of the major obstacles to successful cancer chemotherapy, and the mechanism of MDR is unknown yet. In this work, models of the kinetics of drug uptake and efflux of Dox for K562 cells and K562/A cells were set up to study the mechanism of MDR, and the relationship between kinetic parameters {R) and Reversal Index (Rl) for reversers was examined to discuss whether it was reasonable for R to evaluate the reversal effect of each reverser and to screen the reversers.In order to meet the needs of setting up the kinetic models, a method using RP-HPLC with fluorescence detector was developed for determining both the intracellular and the extracellular concentrations of Dox. The proposed method has been verified to be simple, accurate and sensitive. It has low limit of determination, wide linear range, satisfied precision, and good mean recovery.Models for the kinetics of drug uptake and efflux of Dox was set up for both K562 cells and K562/A cells. It included the mechanism model and the regression model. As for K562/A cells, the effects on the models of several reversers, such as VRP, TMP, VRP-TMP, Pae, Que, SW, and SM were determined. It had clearly shown that all of the selected reversers could increase the cellular membrane's permeation coefficients of Dox to some extent, and that the reversers, such as VRP, VRP-TMP, Pae, Que, SW, and SM, could increase the active drug efflux coefficients of Dox by Pgp pump to varied extent. Therefor, it is reasonable to use the kinetic models in studying the reveral mechanism of MDR.Finally, Rl value of each reverser was calculated. The relationship between R and Rl for VRP, VRP-TMP, Pae, Que, SW, and SM was examined. It suggested that there was a linear relationship between Rl and 1/(1+R) or between Rl and In (InR) for K562/A cells, which means that the Rl will decrease when R increases. It also indicated that R could be used to evaluate the reversal ability of reversers and to screen reversers.
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