Abstract
Subunit of isocitrate dehydrogenase 3 (IDH3a) as upstream of the hypoxia-inducible factor was reported highly expressed in malignant tumors, playing an important role in glucose metabolism reprogramming. As one of rate-limiting enzyme in the Krebs cycle, whether high expression of IDH3a affects glucose uptake in tumors has not been elucidated. This study was aimed to investigate the relationship between IDH3a expression and tumor glucose uptake. Sixty-five patients who underwent 2-[18 F]-2-deoxy-D-glucose ([18 F]-FDG) positron emission tomography/computed tomography (PET/CT) imaging before surgery and pathologically diagnosed as lung adenocarcinoma were included. All patients were divided into high (n = 31) and low (n = 34) groups according IDH3a expression by immunohistochemistry. Comparatively higher [18 F]-FDG uptake was found in high IDH3a expression group. Glucose transporter 1 (GLUT1) level was demonstrated to correlate with IDH3a expression, but not for hexokinase 2 (HK2). Furthermore, A549 and H1299 cells experiment showed, the expression of p-AKT and GLUT1 were significantly downregulated after IDH3a interference. The cellular uptake of [18 F]-FDG and lactate production were significantly reduced in treatment group. In summary, high expression of IDH3a in lung adenocarcinoma patients is associated with higher glucose uptake. IDH3a targets AKT-GLUT1 pathway to affect glucose uptake and metabolites in lung adenocarcinoma.