Enhanced Sensitivity of Nonsmall Cell Lung Cancer with Acquired Resistance to Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors to Phenformin: The Roles of a Metabolic Shift to Oxidative Phosphorylation and Redox Balance

Figure 2

Decreased glycolysis activity in acquired EGFR-TKI-resistant lung cancer. (a) Relative glucose consumption by 2-DG uptake assay. Data represent (, , vs. 2-DG uptake in parental cell line). (b) Glucose contents in culture media. Glucose level was determined by GC-MS in culture media from HCC827 and HCC827 GR cells incubated for 24 h. Glucose concentration was normalized by total protein amounts. Data represent (, vs. HCC827). (c) ECAR changes. ECAR values were obtained from glycolysis stress test using XFp analyzer. Glucose (10 mM), oligomycin (1 μM), and 2-DG (50 mM) were added at indicated time points. Data represent (, , , vs. parental cell line). (d) Basal protein expression levels of glycolysis enzymes. Protein expression of hexokinase (HK)1, HK2, GAPDH, phosphor-PKM2 (Tyr105), PKM2, and phospho-PDHA1 (Ser293) was assessed by immunoblottings.

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