Abstract
Triple-negative breast cancer (TNBC) cells obtain energy mainly through aerobic glycolysis, and their glycolytic rate is significantly higher compared with that of non-TNBC cells. Glucose transporter 1 (GLUT1) is a transmembrane transporter necessary for the entry of glucose into tumor cells, hexokinase (HK) is a key enzyme in the glycolytic pathway, and both are targets of the transcription factor c-Myc. c-Myc can promote aerobic glycolysis by upregulating GLUT1 expression and enhancing HK activity. c-Myc and GLUT1 are highly expressed in TNBC. The non-steroidal anti-inflammatory drug diclofenac can inhibit glycolysis in melanoma cells and thereby promote apoptosis by downregulating c-Myc and GLUT1. To explore the effect of diclofenac on the energy metabolism of TNBC cells and determine the underlying mechanism, a comparative study in two TNBC cell lines (MDA-MB-231 and HCC1937) and one non-TNBC cell line (MCF-7) was conducted. Cell proliferation was detected by Cell Counting Kit-8 (CCK-8) and flow cytometric assays; GLUT1 and c-Myc expression was measured by western blotting. Diclofenac significantly inhibited cell proliferation, downregulated GLUT1 and c-Myc expression, and decreased HK activity in TNBC cells compared with non-TNBC cells. In conclusion, the studies suggested that diclofenac inhibited cell glycolysis and suppressed TNBC cell growth by decreasing GLUT1 protein expression and HK activity through the c-Myc pathway.