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Development and characterization of the P- glycoprotein 1 (Pgp1 ; ABCB1) mediated doxorubicin-reistant PLHC-1 hepatoma fish cell line

Similar to the MDR of mammals, aquatic organisms express Ppg1 and MRP-like proteins as important part of the multi-xenobiotic resistance (MXR) mechanism. Recently we demonstrated the presence of the ABC transport proteins in frequently used fish model, fish hepatoma cell line PLHC-1. In this study we selected highly resistant PLHC-1 cells (PLHC- 1/dox) by culturing them in the presence of doxorubicin. The 42 fold higher expression of ABCB1 gene was measured in PLHC-1/dox cells compared to non-selected cells (PLHC-1/wt). The efflux rates of model fluorescent Pgp1 substrates were 3-4 fold lower in PLHC-1/dox in comparison to PLHC-1/wt cells. Using MTT viability assay we showed that PLHC-1/dox are 45 fold more resistant to doxorubicin than PLHC-1/wt. Furthermore, similarly to mammalian cell lines, typical cross-resistance to other chemotherapeutics like daunorubicin, vincristine, vinblastine and colchicine, was developed. These data prove that specific, highly inducible Pgp1 mediated MXR mechanism is present in the PLHC-1 fish hepatoma cell line.

Pgp ; doxorubicine resistance ; PLHC-1

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