ANALYSIS OF BIOCHEMICAL AND TRANSPORT PROPERTIES OF MULTIDRUG RESISTANCE PROTEIN MRP7 (ABCC10) ON ABCC10-OVEREXPRESSED CaCo2 CELLS
ABC proteins (ATP-dependent proteins) are one of the largest classes of membrane proteins involved in the biological mechanisms of various diseases such as cancer, malaria, leishmaniasis, and some liver diseases. Some of the members of ABCC transporters are involved in the mechanism of multidrug resistance (MDR) against anticancer agents. Currently, the effect of MDR as a defense reaction of tumor cell populations to a range of substances remains a major problem in chemotherapy of cancer. There are a number of mechanisms of multidrug resistance which depend on the stage of the impact of the drug on cells: from the limitation of accumulation of the drug compounds within cells to the cancellation of the programmed death of cells. However, the most studied mechanism is the activation of transmembrane transport proteins which can remove different substances (including widely known P-glycoprotein (ABCB1) and MRP7 (ABCC10) under our consideration) from cells. Thus, the aim of this work was to study the biochemical and transport properties of the multidrug resistance protein ABCC10. In the experiments, we used CaCo2 cells (epithelial cells of human adenocarcinoma): two cell clones transfected with ABCC10 and a control line transfected with empty vector. It was found that ABCC10 localizes in the membranes of CaCo2 cells, taking a basolateral position. It was also revealed that ABCC10-transfected clones of CaCo2 cells show lower ability to accumulate docetaxel compared to the control cell line, which is more sensitive to the drug. Based on the results, we can conclude that ABCC10 is a membrane efflux pump of docetaxel as a substrate in CaCo2 cells.