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

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International Institute of Anticancer Research, NAOYA, KAMIYAMA ; SAORI, TAKAGI ; CHIAKI, YAMAMOTO ; TAKEAKI, KUDO ; TAKAHITO, NAKAGAWA ; MASATO, TAKAHASHI ; KAZUAKI, NAKANISHI ; HIROMASA, TAKAHASHI ; SATORU, TODO ; KEN, ISEKI, ANTICANCER RESEARCH, 26(2A), 2006, 885-888.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.