Influence of Dichloroacetate on Wilms'Tumor in vitro

Abstract

Objective: To investigate the effect of dichloroacetate (DCA) on Wilms' tumor (WT) G401 cells.

Methods: CCK-8 assay was used to detect the influence of DCA on G401 cells viability and 10 mmol/L DCA was selected for subsequent experiments. The expression of glycolysis-related enzymes, such as hexokinase 2 (HK2), pyruvate kinase M2 (PKM2), lactic acid dehydrogenase A (LDHA), pyruvate dehydrogenase kinase 1 (PDK1), and pyruvate dehydrogenase (PDH), were detected by qRT-PCR and western blot. The extracellular lactic acid and glucose concentrations were measured by the lactic acid assay kit and glucose oxidase method kit respectively. Flow cytometry was used to detect the effect of DCA on G401 cells apoptosis. The invasion and migration ability of G401 cells were detected by Transwell assay and wound-healing assay.

Results: The results showed that DCA reduced glycolysis-related enzymes expression, inhibited lactic acid production, and glucose consumption. DCA also suppressed cells growth, induced cells apoptosis and inhibited cells invasion and migration.

Conclusion: Inhibition of aerobic glycolysis by DCA can reduce the viability of G401 cells, promote cells apoptosis and inhibit cells invasion and migration. Therefore, aerobic glycolysis may be a potential therapeutic target for Wilms' tumor.

Keywords: Wilms’ tumor; aerobic glycolysis; dichloroacetate.