Background/purpose: A common trait among cancers is the increased level of glycolysis despite adequate oxygen
levels to support aerobic respiration. This has been shownrepeatedly in different humanmalignancies.Glycolysis
inhibitors, especially 3-bromopyruvate, have been shown to be effective chemotherapeutic agents. The effect of
glycolysis inhibition upon chemotherapy resistance is relatively unknown.
Methods: Wild-type and doxorubicin-resistant lines of neuroblastoma (SK-N-SH and SK-N-Be(2)C)were used in
this study. Using anMTT assay, the IC50 of 3-BrPA was determined. Subsequently, doxorubicin-resistant cell lines
were treated with 3-bromopyruvate, doxorubicin, and 3-bromopyruvate with doxorubicin. Additionally, a
luminescence ATP detection assay was used to measure intracellular ATP levels, and a lactate assay was used to
determine intracellular lactate levels. All experiments were repeated in hypoxic conditions.
Results: Treatmentwith 3-bromopyruvate and doxorubicin significantly decreased the mean cell viabilities at 24,
48, and 72 hours in normoxic conditions. A similar response was replicated in hypoxic conditions. Treatment
with 3-bromopyruvate significantly decreased intracellular ATP and lactate levels.
Conclusion: Glycolysis inhibitors such as 3-bromopyruvate could prove to become an effective means by which
chemotherapy resistance can be overcome in human neuroblastoma.