Purpose: To determine whether protein kinase C-iota (PKC-iota) is associated with glucose metabolism in non-small-cell lung cancer (NSCLC) and whether its regulatory effect on metabolic and biological changes observed in NSCLC can be mediated by glucose transporter 1 (GLUT1).
Patients and methods: Forty-five NSCLC patients underwent combined 18F-fludeoxyglucose (18F-FDG) positron emission tomography and computed tomography (PET/CT) before surgery, and another eighty-one NSCLC patients were followed-up for 1-91 months after tumor resection. The rate of glucose metabolism in NSCLC was quantified by measuring the maximum standardized uptake value (SUVmax) by 18F-FDG PET/CT. PKC-iota and GLUT1 in NSCLC were detected by immunostaining. In vitro, PKC-iota was knocked down, whereas GLUT1 was silenced with or without PKC-iota overexpression to identify the role of PKC-iota in glycolysis. Spearman's rank correlation coefficient was used in the correlation analysis. Kaplan-Meier analysis was used to assess survival duration.
Results: There was a positive relationship between PKC-iota expression and SUVmax in NSCLC (r=0.649, P<0.001). PKC-iota expression also showed a positive relationship with GLUT1 in NSCLC tissues (r=0.686, P<0.001). Patients whose NSCLC tissues highly co-expressed PKC-iota and GLUT1 had worse prognosis compared with patients without high co-expression of PKC-iota and GLUT1. In vitro, PKC-iota silencing significantly decreased the expression of GLUT1 and inhibited glucose uptake and glycolysis; c-Myc silencing restrained PKC-iota-mediated GLUT1 elevation; GLUT1 knockdown remarkably suppressed PKC-iota-mediated glycolysis and cell growth.
Conclusion: In NSCLC, the rate of glucose metabolism was positively correlated with PKC-iota expression. PKC-iota increased glucose accumulation and glycolysis by upregulating c-Myc/GLUT1 signaling and is thus involved in tumor progression.
Keywords: 18F-fludeoxyglucose; glucose transporter 1; glycolysis; non-small-cell lung cancer; protein kinase C-iota.