The effect of oestrogens and medroxyprogesterone acetate on the uptake of cytotoxic drugs by MCF-7 breast cancer cells.
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.
Reed
M J
MJ
Unit of Metabolic Medicine, St. Mary's Hospital Medical School, Imperial College of Science, Technology and Medicine, London, U.K.
Ross
M S
MS
Ghilchik
M W
MW
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008525:Medroxyprogesterone / Q000031:analogs & derivatives* / Q000494:pharmacology; D017258:Medroxyprogesterone Acetate; D008727:Methotrexate / Q000493:pharmacokinetics* / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014750:Vincristine / Q000493:pharmacokinetics* / Q000494:pharmacology
D000970:Antineoplastic Agents; D004967:Estrogens; D014750:Vincristine; D017258:Medroxyprogesterone Acetate; D008525:Medroxyprogesterone; D008727:Methotrexate