Effect of methotrexate on the intracellular phosphoribosyl pyrophosphate level and glucose transport of Ehrlich ascites tumor cells in vitro.
Methotrexate (MTX) suppressed the growth of Ehrlich ascites tumor (EAT) cells in vitro. The intracellular level of phosphoribosyl 5-pyrophosphate (PRPP) of EAT cells increased in a dose-dependent manner in response to MTX treatment. At the same time, the rate of glucose transport was lowered. Hypoxanthine reversed both these effects of MTX and partially rescued EAT cell growth. Under all conditions tested, changes in rate of glucose transport were shown to be the result of alterations in the number of glucose transporter (Vmax) rather than ligand affinity (Km). The dual action of MTX as a chemotherapeutic agent is discussed in this light.
Fung
K P
KP
Department of Biochemistry, Chinese University of Hong Kong, Shatin, Hong Kong.
Lam
W P
WP
Choy
Y M
YM
Lee
C Y
CY
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D002286:Carcinoma, Ehrlich Tumor; D002455:Cell Division / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000494:pharmacology; D008727:Methotrexate / Q000494:pharmacology*; D010754:Phosphoribosyl Pyrophosphate / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000964:Antimetabolites, Antineoplastic; D007042:Hypoxanthines; D019271:Hypoxanthine; D010754:Phosphoribosyl Pyrophosphate; D005947:Glucose; D008727:Methotrexate