Dual inhibition of oxidative phosphorylation and glycolysis exerts a synergistic antitumor effect on colorectal and gastric cancer by creating energy depletion and preventing metabolic switch
Fig 1
Metabolic and antitumor effect of the LDH inhibitor NCI-006 and the mitochondrial complex I inhibitor IACS-010759 in HCT116 and MKN45 cells.
(A)The metabolic activities in response to treatment were determined according to the OCR/ECAR levels of HCT116 and MKN45 cells with or without treatment. Dashed lines connect the baseline activity (0 min; open symbols) and metabolic activity after treatment (100 min; closed symbols); IACS-010759 at 2 μM and/or NCI-006 at 5 μM were applied. Data are displayed as the mean ± SD. (B)The ATP production rate was measured using the XF Real-Time ATP Rate Assay Kit (Agilent Technologies, Santa Clara, CA, USA) according to the OCR/ECAR levels in HCT116 and MKN45 cells with or without treatment. Data are displayed as mean ± SD (*p < 0.05, **p < 0.01, two-way ANOVA Tukey test). (C)HCT116 and MKN45 cells were treated with NCI-006 (1 μM) and/ or IACS-010759 (1 μM) for 48 h, and cell proliferation was assessed. Data are displayed as means ± SD (n = 18 for each group; **p < 0.01, two-way ANOVA Tukey test). ECAR, Extracellular Acidification Rate.