Abstract
1469
Objectives: We have previously demonstrated that low concentrations (0.1 mg/ml) of 2-Deoxyglucose (2-DG) have significant therapeutic effects on a variety of human cancer cell lines. In order to understand the mechanisms underlying the effects of 2-DG we evaluated in-vitro exogenous glucose utilization and cellular proliferation during 2-DG treatment. Methods: Two NSCLC cell lines (H3255 and HCC4006) with different degrees of sensitivity to 2-DG treatment were studied. To measure the effects of 2-DG treatment on glucose utilization and cellular proliferation, 1 x 105 cells were plated in media with 2 mg/ml glucose and uptakes of F18-fluorodeoxyglucose (FDG) and F18-fluorothymidine (FLT) were measured before and after treatment with 0.1 mg/ml 2-DG for three days. 2-DG was not present during the FDG/FLT uptake experiments. The intracellular radiotracer concentration was calculated by dividing the total sample FDG or FLT uptake by the total cellular volume, which was determined by measurements of cell diameters and total cell number with a Beckman Coulter Counter. The degree of growth inhibition was measured by counting the number viable, trypan blue negative treated cells, relative to controls. Results: As expected from previous experiments, 2-DG treatment was more effective in HCC4006 than in H3255 cells (reduction in the number of viable cells 50% vs. 35%, respectively). This corresponded to an approximately 2-times higher baseline FDG-uptake in HCC4006 as compared to H3255 cells. However, 2-DG treatment had only a minor impact on FDG-uptake. Treatment with 0.1 mg/ml 2-DG for 3 days reduced FDG uptake by 14% in HCC4006 (p=NS) and by 24% in H3225 (p=NS). In contrast, 2-DG treatment markedly reduced FLT uptake by 49% in HCC4006 (p<0.001) and by 22% in H3255 (p=0.05). Conclusions: These results imply that in cells with a high baseline FDG uptake, 2-DG at a low concentration (1/10th of the normal plasma concentration) that only minimally inhibits glucose metabolism significantly inhibits cellular proliferation. These findings warrant further testing of 2-DG treatment in tumor models with high glycolytic activity.
- Society of Nuclear Medicine, Inc.