PMID: 16619483Apr 20, 2006Paper

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

Anticancer Research
Naoya KamiyamaKen Iseki

Abstract

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. 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. 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. 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.

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