Effects of antitumor agents on 3H-2-deoxyglucose uptake in tumor cells and their relationship with the main targets of the antitumor agents.
To investigate the effects of antitumor drugs on 3H-2-deoxyglucose (DG) uptake in tumor cells, we performed DG uptake studies of the short-term treatment of four kinds of antitumor drugs in a cell culture system. The antitumor drugs adriamycin (ADM) and cisplatin (cDDP), which affect on DNA synthesis, did not greatly affect DG uptake, but DG uptake was lowered by antitumor drugs, actinomycin D (AcD) and cycloheximide (CHX), which target the gene expression system. To investigate the mechanism of DG uptake changes, we also tested the effects of some glucose metabolic inhibitors on DG uptake. An inhibitor of glycolytic flow (iodoacetate) lowered DG uptake whereas mitochondrial inhibition increased DG uptake. These results on the inhibition of glucose metabolism indicated that there were two types of factors affecting DG uptake directly; one affects glycolysis and the other affects oxidative phosphorylation. The two antitumor drugs with effects on gene expression were thought to act by the former. The effects of the drug treatments for tumors on DG uptake could be divided into three groups; glycolysis inhibition, mitochondrial inhibition and no relation to glucose metabolism. With the further observations of FDG uptake changes based on this prediction, the biochemical relationship between treatment effects and FDG uptake changes will be clarified.
Waki
A
A
Biomedical Imaging Research Center, Fukui Medical School, Japan.
Fujibayashi
Y
Y
Sadato
N
N
Tsuchida
T
T
Ishii
Y
Y
Yokoyama
A
A
Yonekura
Y
Y
D019297:2,4-Dinitrophenol / Q000494:pharmacology; D000230:Adenocarcinoma / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000032:analysis; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002945:Cisplatin / Q000494:pharmacology; D003847:Deoxyglucose / Q000493:pharmacokinetics*; D004317:Doxorubicin / Q000494:pharmacology; D004347:Drug Interactions; D006151:Guanosine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D006801:Humans; D007461:Iodoacetates / Q000494:pharmacology; D019807:Iodoacetic Acid; D019344:Lactic Acid / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000378:metabolism
D000970:Antineoplastic Agents; D007461:Iodoacetates; C037626:3'-O-methylguanosine; D006151:Guanosine; D019344:Lactic Acid; D004317:Doxorubicin; D000255:Adenosine Triphosphate; D003847:Deoxyglucose; D019297:2,4-Dinitrophenol; D002945:Cisplatin; D019807:Iodoacetic Acid