Expression of ABC transporters in human hepatocyte carcinoma cells with cross-resistance to epirubicin and mitoxantrone.

BACKGROUND In order to understand the cross-resistance between epirubicin (EPI) and mitoxantrone (MIT), EPI- and MIT-resistant cells were established and their cross-resistance was evaluated. MATERIALS AND METHODS The degrees of growth inhibition of EPI-resistant HLE-EPI cells and MIT-resistant HLE-MIT cells by anticancer drugs were measured. The mRNA expressions of multidrug resistance protein 1 (MDR1)/ABCB1 and breast cancer resistance protein (BCRP)/ABCG2 were also measured by quantitative real-time RT-PCR. Moreover, intracellular accumulation of EPI was investigated. RESULTS HLE-EPI cells were resistant to EPI, MIT and docetaxel. HLE-MIT cells were resistant to EPI, MIT and SN-38. HLE-EPI cells overexpressed MDR1 and HLE-MIT cells overexpressed BCRP. The intracellular accumulation of EPI was decreased in HLE-EPI and HLE-MIT cells. CONCLUSION The results suggest that both MDR1 and BCRP can up-regulate the efflux of EPI causing resistance to EPI in HLE-EPI and HLE-MIT cells.