Effect of 5-fluorouracil on methotrexate transport and cytotoxicity in HT29 colon adenocarcinoma cells.
Exposure of the human colon adenocarcinoma HT29 cells to different concentrations of 5-fluorouracil (5FU) for 24 h resulted in a dose-dependent increase in the cellular glutathione (GSH) level which remained elevated up to 72 h following 5FU treatment. Pretreatment of HT29 cells with 5FU was found to enhance the uptake of methotrexate (MTX) as compared to control cells. Administration of MTX 24 h after 5FU was found to be synergistic, whereas administration of MTX 24 h before 5FU or together with 5FU was not found to be synergistic. The results of this study suggest that the increase in cellular GSH level as a result of 5FU pretreatment may play a role in the enhancement of MTX uptake and the cytotoxicity of both drugs in HT29 cells.
Chen
M F
MF
Department of Internal Medicine, University of South Florida College of Medicine, Tampa 33612-4799.
Chen
L T
LT
Boyce
H W
HW
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism*; D001692:Biological Transport; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D004334:Drug Administration Schedule; D004357:Drug Synergism; D005472:Fluorouracil / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D008727:Methotrexate / Q000493:pharmacokinetics* / Q000633:toxicity*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D005978:Glutathione; D005472:Fluorouracil; D008727:Methotrexate