Role of ABC Transporters in the BeWo Trophoblast Cell Line

ABSTRACT

The transport of doxorubicin and rhodamine 123, substrates of ABC transporters, was evaluated in the BeWo stabilized trophoblast cell line. Both compounds were taken up by BeWo cells, but their intracellular concentrations were highly dependent on temperature, and significantly reduced at 4°C. The P-glycoprotein inhibitors verapamil and PSC833 did not modify the intracellular concentrations of the two substrates, suggesting therefore that, in these cells, the activity of P-glycoprotein is not important. MK571, which inhibits MRPs, was on the contrary effective in increasing rhodamine 123 intracellular concentrations. The efflux of both fluorescent substrates was extremely slow, and slightly reduced by MK571. Finally, a polarized transport of doxorubicin from basal to apical side was evident, although only during the first 60 min of incubation, and was reduced by P-glycoprotein, MRP, and BCRP inhibitors. No MDR1 expression was revealed at the mRNA and protein levels; on the contrary, MRP1 and BCRP were expressed in these cells. In BeWo cells the activity of ABC transporters, and in particular of P-glycoprotein, seems to be extremely limited.

KEYWORDS:

• BeWo cells
• Multidrug resistance-related proteins
• Multidrug transporters
• P-glycoprotein
• Placenta