Fig. 3

Effects of MCT1 and MCT4 on biological behaviors of tumor cells under different conditions including hypoxia, high concentration of extracellular lactate and inhibition of oxidative respiration. A Extracellular lactate levels in MNNG/HOS and U-2 OS cells treated with DMSO under normoxia, or with DMSO, 10 µM AZD3965 (AZD), 10 µM VB124 (VB) and AZD + VB under hypoxia for 2 h (n = 5). “24 h” means cells were pretreated as above for 24 h and then extracellular lactate level was measured 2 h after replacement of culture medium. B Protein expression of MCT1 and MCT4 in cells treated with DMSO under normoxia, or DMSO, AZD3965, VB124 and AZD + VB under hypoxia. C Protein expressions of HIF-1α and c-Myc in cells incubated under normoxia or hypoxia. D Lactate consumption in cells treated with DMSO, AZD3965, VB124 and AZD + VB for 24 h in low-glucose (500 mg/L) medium containing 20 mM lactate. E Cell proliferation analysis after treatment with DMSO, AZD3965, VB124 and AZD + VB in culture medium with or without 20 mM lactate for 3 days. F Cell proliferation assay in cells treated with DMSO, AZD3965, VB124 and AZD + VB, with or without 0.1 µM oligomycin (mitochondrial oxidative phosphorylation inhibitor) for 3 days. Data are shown as mean ± standard deviation (SD). In groups with treatment for 2 h, statistical differences are compared to normoxia group. In the groups with treatment for 24 h, statistical differences are obtained by comparing with corresponding group of 2-h treatment (A). In D–F, statistical differences are calculated by comparing to DMSO group or as indicated. *p < 0.05, **p < 0.01, ***p < 0.001; ns, not significant