Reversal Effects of Ivermectin and Moxidectin on Multidrug Resistance in C6/adr Cells in vitro

Multidrug resistance（MDR） is a serious obstacle encountered in cancer treatment. This study was performed to explore the reversal MDR activity of ivermectin（IVM） from avermectin family and moxidectin（MOX） belonging to milbemycin family. The two compounds(5 μmol · L^-1) showed strong potency to increase adriamycin cytotoxicity toward adriamycin-resistant rat glioma cells C6/adr with fold reversal（FR） of 31.02 and 13.40, respectively. In addition, the mechanisms of them on p-glycoprotein（P-gp）-mediated MDR demonstrated that the two compounds significantly increased the intracellular accumulations of adriamycin and Rh123 via inhibiting P-gp efflux. Based on the analysis of P-gp, MDR1 and MRP1 gene expressions by using immunofluorescence flow cytometry and RT-PCR, the results revealed that the two compounds could down regulate the expression of P-gp, and that MDR1 and MRP1 gene expressions were down regulated. These findings suggested that ivermectin and moxidectin probably represented potent agents for reversing MDR in cancer therapy, and especially ivermectin was a better modulator.