Metabolism of Human Leukemia Cells in NOD/Scid Mice: Effectiveness of 2-Deoxy-D-Glucose

Abstract 4881

We have recently shown that NB4,an APL cell line, is dependent on glycolysis, while THP-1, a monocytic cell line, is relatively dependent on oxidative phosphorylation in mitochondria, where oxidation of fatty acid is important. (Leukemia and Lymphoma 51:2112,2010)

Here, we examined the energy metabolism of these leukemia cell lines in immunodeficient mice. 1.0×10⁷ cells of each cell line were inoculated subcutaneously in NOD/scid mice with the treatment of anti-asialo GM1 antibody. Mice were divided into two groups: normal diet (carbohydrate;65.3%, fat;6.3%) or carbohydrate-restricted (high fat) diet (carbohydrate;19.6%, fat;62.2%). At day 42, tumor volume (TV) of NB4 in three normal diet-fed mice became 694±358mm³, which was greater than that in three high fat diet-fed mice:173±216mm³ (P= 0.043). On the other hand, tumor volume of THP-1 in three normal diet-fed mice became 1130 ± 600mm³, which was smaller than that in three high fat diet-fed mice: 3300 ± 1053mm³ (p = 0.050).

Then, since 14 days after inoculation of leukemia cells in NOD/scid mice fed with normal diet, glycolysis inhibitor 2-deoxy-D-glucose (2-DG) (35mg/mouse) was administered intraperitoneally once a week. Tumor size at day 41 of both leukemia cells were suppressed by 2-DG treatment. (THP-1: 2-DG (-): TV = 3099 ± 193mm³, 2-DG (+): TV = 513 ± 550mm³) (THP-1: p = 0.040). (NB4: 2-DG (-): TV = 495 ± 417mm³, 2-DG (+): TV = 87 ± 89mm³) (NB4: p = 0.313).

Pathological examination of tumors have shown that 2-DG treated tumor had larger areas of dead cells in both cell lines.

Our study demonstrated that NB4 is dependent largely on glucose and THP-1 on fat. In addition, 2-DG is effective in growth suppression of leukemia cells in vivo. These findings will help the future therapy for leukemia targeting energy metabolism.