PMID- 33850556 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210416 IS - 1792-0981 (Print) IS - 1792-1015 (Electronic) IS - 1792-0981 (Linking) VI - 21 IP - 6 DP - 2021 Jun TI - Diclofenac impairs the proliferation and glucose metabolism of triple-negative breast cancer cells by targeting the c-Myc pathway. PG - 584 LID - 10.3892/etm.2021.10016 [doi] LID - 584 AB - 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. CI - Copyright: (c) Yang et al. FAU - Yang, Lihui AU - Yang L AD - Department of Nursing, Guangxi Medical University Nursing College, Nanning, Guangxi 530021, P.R. China. FAU - Li, Jiachen AU - Li J AD - Department of Clinical Medicine, Guangxi Medical University The First Clinical Medical College, Nanning, Guangxi 530021, P.R. China. FAU - Li, Yongzhuo AU - Li Y AD - Department of Medicine Guangxi University Medical College, Nanning, Guangxi 530004, P.R. China. FAU - Zhou, Yongli AU - Zhou Y AD - Department of Clinical Medicine, Guangxi Medical University The First Clinical Medical College, Nanning, Guangxi 530021, P.R. China. FAU - Wang, Ziqian AU - Wang Z AD - Department of Clinical Medicine, Guangxi Medical University The First Clinical Medical College, Nanning, Guangxi 530021, P.R. China. FAU - Zhang, Dahao AU - Zhang D AD - Department of Clinical Medicine, Guangxi Medical University The First Clinical Medical College, Nanning, Guangxi 530021, P.R. China. FAU - Liu, Jinlu AU - Liu J AD - Department of Gastrointestinal and Gland Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China. FAU - Zhang, Xiaodong AU - Zhang X AD - Department of Gastrointestinal and Gland Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China. LA - eng PT - Journal Article DEP - 20210402 PL - Greece TA - Exp Ther Med JT - Experimental and therapeutic medicine JID - 101531947 PMC - PMC8027724 OTO - NOTNLM OT - GLUT1 OT - c-Myc OT - diclofenac OT - glycolysis OT - triple-negative breast cancer COIS- The authors declare that they have no competing interests. EDAT- 2021/04/15 06:00 MHDA- 2021/04/15 06:01 PMCR- 2021/04/02 CRDT- 2021/04/14 06:32 PHST- 2020/06/17 00:00 [received] PHST- 2021/02/26 00:00 [accepted] PHST- 2021/04/14 06:32 [entrez] PHST- 2021/04/15 06:00 [pubmed] PHST- 2021/04/15 06:01 [medline] PHST- 2021/04/02 00:00 [pmc-release] AID - ETM-0-0-10016 [pii] AID - 10.3892/etm.2021.10016 [doi] PST - ppublish SO - Exp Ther Med. 2021 Jun;21(6):584. doi: 10.3892/etm.2021.10016. Epub 2021 Apr 2.