Influence of 2-deoxy-D-glucose and arterial ischaemia on glucose oxidation and growth of liver cancer in the rat.
Malignant tissues are known to exhibit a high rate of glucose oxidation. It could therefore be hypothesized that reduction of glucose oxidation could be of benefit for the treatment of malignancies. We tested this approach, and by using [UL14C]glucose, we showed that glucose oxidation in a transplanted adenocarcinoma in the rat liver was 2.81 +/- 0.23 times as high as that of the surrounding liver tissue (P less than 0.01). In vivo treatment with intra-arterial 2-deoxy-D-glucose (2DG) infusion at 800 mg/kg via the gastroduodenal artery reduced the tumour/liver ratio of glucose oxidation to 1.88 +/- 0.12 (P less than 0.01). A similar inhibition of tumour glucose oxidation was obtained by 1 h of hepatic arterial ischaemia (P less than 0.05), or by ischaemia combined with 2DG infusion at 400 mg/kg (P less than 0.01). A 5-day course of intermittent hepatic dearterialization combined with continuous intra-arterial 2DG infusion at 400 mg/kg/day produced liver tumour growth retardation (P less than 0.01). We conclude that intermittent dearterialization reduces not only tumour growth but also the high tumour glucose oxidation. Dearterialization reduced glucose oxidation as much as 2DG did, which could be a mechanism behind reduced tumour growth.
Mack
P
P
Department of Surgery, Lund University, Sweden.
Ahrén
B
B
Jeppsson
B
B
Kan
Z
Z
Bengmark
S
S
D000230:Adenocarcinoma / Q000378:metabolism; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D003837:Deoxy Sugars / Q000494:pharmacology*; D003847:Deoxyglucose / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D007511:Ischemia / Q000378:metabolism; D008099:Liver / Q000098:blood supply* / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D051381:Rats; D011920:Rats, Inbred WF
D003837:Deoxy Sugars; D003847:Deoxyglucose; D005947:Glucose