Signal transducer and activator of transcription 3 promotes the Warburg effect possibly by inducing pyruvate kinase M2 phosphorylation in liver precancerous lesions

Figure 4 Activated signal transducer and activator of transcription 3 promotes the Warburg effect by enhancing p-pyruvate kinase M2 in transformed WB-F344 cells. A-C: The glucose concentration in medium in transformed WB-F344 cells induced with N-methyl-N'-nitro-N-nitroso-guanidine (MNNG) + hydrogen peroxide (H₂O₂) was lower than that in control WB-F344 cells. The lactate concentration in medium in transformed WB-F344 cells induced with MNNG + H₂O₂ was higher than that in control WB-F344 cells. Inhibition of p-signal transducer and activator of transcription 3 resulted in suppression of glucose consumption, lactate production, and ATP level. TEPP-46 and pyruvate kinase M2 (PKM2) siRNA further reduced the Warburg effect. D: The activation of p-PKM2 was elevated in transformed WB-F344 cells induced with MNNG + H₂O₂ and was inhibited following stattic treatment. Stattic, TEPP-46, and PKM2 siRNA inhibited the expression of p-PKM2 in transformed WB-F344 cells induced with MNNG + H₂O₂. E: The expression and nuclear translocation of PKM2 were elevated in transformed WB-F344 cells induced with MNNG + H₂O₂ and were inhibited following stattic treatment. (^aP < 0.05, ^bP < 0.01) (stattic: 4 μmol/L, 48 h; TEPP-46: 25 μmol/L, 24 h). MNNG: N-methyl-N'-nitro-N-nitroso-guanidine; H₂O₂: Hydrogen peroxide; STAT3: Signal transducer and activator of transcription 3; PKM2: Pyruvate kinase M2.