Research Paper Volume 11, Issue 23 pp 11329—11346

Interplay of MKP-1 and Nrf2 drives tumor growth and drug resistance in non-small cell lung cancer

Figure 2. MKP-1 regulates metabolism of A549 NSCLC cells and promotes tumor growth. (A) Representative images and weights of tumors 6 weeks after subcutaneous injection of siMKP1-C1, siMKP1-C2 or siCon cells into Nu/Nu mice. Values are mean ± SD, n = 8. (B) MKP-1 knockdown alters glucose and glutamine metabolism in A549 Cells. siMKP1-C1, siMKP1-C2 and siCon cells were cultured for three days before glucose consumption, lactate production, citrate, NADPH, G6PD activity, and GSH levels were determined. The value for culture medium at day 0 was set at 100% for the analysis of glucose consumption. The value for siCon cells was set at 100% for the analysis of GSH levels. Values are mean ± SD, n = 3, *p <0.05, **p <0.01. (C). MKP-1 regulates glucose and glutamine metabolism in NSCLC cells. Metabolite abbreviations: G6P, glucose 6-phosphate; F6P, fructose 6-phosphate; F1,6P, fructose 1,6-bis-phosphate; GA3P, glyceraldehyde 3-phosphate; 3-PG, 3-phosphoglycerate; PEP, phosphoenolpyruvate; 6-P-Gl, 6-phosphogluconolactone; 6-PG, 6-phosphogluconate; R-5-P, ribulose5-phosphate; PRPP, 5-phosphoribosyl-α-1-pyrophosphate; 5-PRA, b-5-phosphorybosylamine; GSH, reduced glutathione. The metabolic enzymes regulated by MKP-1/Nrf2 in glucose and glutamine metabolisms, are shown in red. G6PD, glucose-6-phosphate dehydrogenase; GCLC, glutamate-cysteine ligase, catalytic subunit; IDH1, isocitrate dehydrogenase 1; ME1, malic enzyme 1; MTHFD2, methylenetetrahydrofolate dehydrogenase 2; PGD, 6-phosphogluconate dehydrogenase; PPAT, phosphoribosyl pyrophosphate amidotransferase; TALDO1, transaldolase1; TKT, transketolase. The mitochondrion is shown in gray.