Inhibitory effect of 2-deoxy-D-glucose on liver tumor growth in rats.

Since tumor cells are more dependent on glycolysis for energy supply than other cells, we tested whether its inhibition by 2-deoxy-D-glucose (2-DG) affects tumor growth. Male Wistar rats were inoculated in the liver with tumor cells from a chemically induced colonic adenocarcinoma. From day 5 after inoculation 2-DG (400 mg/kg/24 h) was continuously infused into the hepatic artery for 5 days; controls received saline in the same fashion. Seven days after the end of infusion, the animals were sacrificed. A second experimental group of rats was treated with isolated liver perfusion for 30 min with oxygenated blood through the portal vein and hepatic artery simultaneously. In the perfusate, 400 mg/kg 2-DG were added, and the rats were sacrificed at 10 days after perfusion. A first control group underwent perfusion without 2-DG, and a second control group received i.v. infusion of 2-DG (400 mg/kg/30 min) for 30 min over 5 days. A nontreated control group was also added. All animals survived the procedures. The concentration of blood glucose increased in the rats receiving 2-DG i.v. and intraarterially but was unchanged in the other groups. The tumor growth was significantly reduced by 2-DG in all experimental groups, with no difference between the groups. It is therefore concluded that 2-DG is of potential interest in the treatment of malignancies. Since local application of 2-DG avoids the risk for systemic side effects, this approach should be explored further.