The effect of oestrogens and medroxyprogesterone acetate on the uptake of cytotoxic drugs by MCF-7 breast cancer cells.

ABSTRACT

Previous studies have shown that human breast cancer cells (MCF-7) show an increased response to a number of cytotoxic drugs after 48 h pretreatment with medroxyprogesterone acetate (MPA). As there is evidence that MPA can influence membrane fluidity, we have examined the effect of pre-treatment with MPA on the uptake of methotrexate (MTX) and vincristine (VCR) by MCF-7 cells. The effect of pre-treatment with oestrogen on cytotoxic drug uptake was also examined. After 48 h pre-treatment with MPA (40 or 160 nmol/L), the uptake of MTX was significantly reduced by 14%-44%. Uptake of VCR was also reduced (10%-16%) after pre-treatment of cells with MPA but to a lesser degree than detected for MTX. Pre-treatment with ethinyloestradiol increased the uptake of MTX by up to 45% but enhanced uptake was only detected in cells after exposure to MTX for 1 h. While the results from this study show that oestrogens or MPA can alter the uptake of cytotoxic drugs by MCF-7 breast cancer cells, it is not clear how the MPA dependent decrease in drug uptake enhances the response of MCF-7 to such drugs previously reported.