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Figure 4. Chemoresistant HR+/HER2- BC cells exhibit reduced mitochondrial respiration and glycolytic capacity. (A and B) OCR profiles in parental and chemoresistant MCF-7 (A) and ZR-75-1 (B) cells following sequential treatment with 1 µM oligomycin, 2 µM FCCP and 0.5 µM rotenone/antimycin A; (C-F) Quantification of basal (C and E) and maximal (D and F) mitochondrial respiration in parental and chemoresistant MCF-7 (C and D) and ZR-75-1 (E and F) cells; (G and H) ECAR profiles in parental and chemoresistant MCF-7 (G) and ZR-75-1 (H) cells following sequential treatment with 10 mM glucose, 1 µM oligomycin and 50 mM 2-DG; (I-L) Quantification of glycolysis (I and K) and maximal glycolytic capacity (J and L) in parental and chemoresistant MCF-7 (I and J) and ZR-75-1 (K and L) cells; (M and N) Seahorse-based energetic maps (i.e., mitochondrial respiration vs. glycolysis) in parental and chemoresistant MCF-7 (M) and ZR-75-1 (N) cells after evaluation of basal OCR and ECAR. Data are presented as mean ± SEM from three independent biological experiments (n = 3), each performed with five technical replicate wells per condition (A-N). Individual data points represent the mean of the technical replicates from each independent biological experiment. Statistical significance was determined using one-way ANOVA with Dunnett’s multiple comparison test (C-F and I-L). ^*P < 0.05; ^**P < 0.01; ^***P < 0.001; ns: not significant. HR+/HER2-: Hormone receptor-positive/human epidermal growth factor receptor 2-negative; BC: breast cancer; OCR: oxygen consumption rate; FCCP: carbonyl cyanide-4 (trifluoromethoxy)phenylhydrazone; ECAR: extracellular acidification rate; 2-DG: 2-deoxyglucose; SEM: standard error of the mean; ANOVA: analysis of variance; Doc-R: docetaxel-resistant; Epi-R: epirubicin-resistant; Pac-R: paclitaxel-resistant.