Synergistic anti-tumor effect of metformin and dichloroacetate in MFCW-ampIified neuroblastoma BE-2C cells / 中国药理学通报

ABSTRACT

To investigate the effect of metformin production of combined group compared with alone combined with dichloroacetate on the proliferation of A/FC/V-amplified neuroblastoma BE-2C cells and its mechanisms. Methods The inhibitory effects of metformin and dichloroacetate alone or in combination on BE-2C cells was measured by CCK-8 assay; the concentrations of glucose and lactic acid in the medium were measured by a glucose test kit and L-lactic acid assay kit; cell apoptosis was determined by flow cytometry (FCM) with Annexin V-FITC conjugated propidium iodide (PI) staining; the expressions of apoptosis related protein were detected by Western blot. Results Metformin and dichloroacetate showed significant proliferation inhibition activity on BE-2C cells; there was obviously decreased glucose uptake and lactic acid production of combined group compared with alone group (P <0. 01) ; the apoptotic rate was significantly higher in combined group compared with that in alone group (P <0. 01) ; Bax and cleaved caspasce-3 protein expression markedly increased in combined group, but Bcl-2 protein expression significantly increased compared with alone group (P <0. 01). Conclusions Metformin combined with dichloroacetate shows a significant synergistic anti-tumor effect against BE-2C cells by reducing the accumulation of lactic acid caused by metformin and inducing apoptosis.