Inhibition of established rat fibrosarcoma growth by the glucose antagonist 2-deoxy-D-glucose.

Abstract

Sarcoma cells exhibit higher rates of glycolysis than normal tissues and may be dependent on glucose utilization for growth. Accordingly, we tested the ability of the glucose antimetabolite 2-deoxy-D-glucose (2-DG) to inhibit the growth of an established methylcholanthrene-induced rat fibrosarcoma in three groups of F344 rats with increasing subcutaneous inoculations of tumor (2 X 10(6) cells, 1 X 10(7) cells, and 1 mm tumor fragments). Rats were randomized to receive 2-DG or saline solution at doses of 0.75 gm/kg, 1.5 gm/kg, or 1.75 gm/kg, beginning 3 days after tumor implantation and continuing for 10 days. Tumors were removed and weighed on day 14. We measured tissue [14C]-2-DG levels in tumor, brain, liver, and muscle after intraperitoneal injection of radiolabeled 2-DG. In these same tissues we determined the activity of glucose-6-phosphatase (G-6-Pase), an enzyme which dephosphorylates the intracellular glycolytic inhibitor 2-DG-6-phosphate, thus reversing the antitumor effect of 2-DG. All groups treated with 2-DG had a significant reduction in tumor weight of 50% to 70% when compared with saline solution-treated controls. Toxicity was substantial at the highest dose of 2-DG, but minimal toxicity was noted at intermediate and low doses. Tumor had the greatest uptake of [14C]-2-DG, with low levels of G-6-Pase leading to prolonged retention and highest tissue levels of radiolabeled 2-DG. Use of 2-DG inhibits established sarcoma growth because it is rapidly transported into tumors, cannot be metabolized after phosphorylation, and is dephosphorylated and released slowly from tumor cells. Rat sarcoma growth is dependent on glucose utilization and can be effectively inhibited by glucose antagonism.

• Authors: K A Kern, J A Norton
• Journal: Surgery (Surgery) Vol. 102 Issue 2 Pg. 380-5 (Aug 1987) ISSN: 0039-6060 [Print] United States
• PMID: 3039679 (Publication Type: Journal Article)

Chemical References

• Deoxy Sugars
• Deoxyglucose
• Glucose-6-Phosphatase
• Glucose

Topics

• Animals
• Deoxy Sugars (therapeutic use)
• Deoxyglucose (administration & dosage, metabolism, therapeutic use)
• Fibrosarcoma (drug therapy, metabolism)
• Glucose (antagonists & inhibitors)
• Glucose-6-Phosphatase (analysis)
• Injections, Intraperitoneal
• Male
• Neoplasm Transplantation
• Rats
• Rats, Inbred F344
• Soft Tissue Neoplasms (drug therapy, metabolism)
• Tissue Distribution