Open Access

Diclofenac impairs the proliferation and glucose metabolism of triple‑negative breast cancer cells by targeting the c‑Myc pathway

  • Authors:
    • Lihui Yang
    • Jiachen Li
    • Yongzhuo Li
    • Yongli Zhou
    • Ziqian Wang
    • Dahao Zhang
    • Jinlu Liu
    • Xiaodong Zhang
  • View Affiliations

  • Published online on: April 2, 2021     https://doi.org/10.3892/etm.2021.10016
  • Article Number: 584
  • Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.
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June-2021
Volume 21 Issue 6

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Yang L, Li J, Li Y, Zhou Y, Wang Z, Zhang D, Liu J and Zhang X: Diclofenac impairs the proliferation and glucose metabolism of triple‑negative breast cancer cells by targeting the c‑Myc pathway. Exp Ther Med 21: 584, 2021.
APA
Yang, L., Li, J., Li, Y., Zhou, Y., Wang, Z., Zhang, D. ... Zhang, X. (2021). Diclofenac impairs the proliferation and glucose metabolism of triple‑negative breast cancer cells by targeting the c‑Myc pathway. Experimental and Therapeutic Medicine, 21, 584. https://doi.org/10.3892/etm.2021.10016
MLA
Yang, L., Li, J., Li, Y., Zhou, Y., Wang, Z., Zhang, D., Liu, J., Zhang, X."Diclofenac impairs the proliferation and glucose metabolism of triple‑negative breast cancer cells by targeting the c‑Myc pathway". Experimental and Therapeutic Medicine 21.6 (2021): 584.
Chicago
Yang, L., Li, J., Li, Y., Zhou, Y., Wang, Z., Zhang, D., Liu, J., Zhang, X."Diclofenac impairs the proliferation and glucose metabolism of triple‑negative breast cancer cells by targeting the c‑Myc pathway". Experimental and Therapeutic Medicine 21, no. 6 (2021): 584. https://doi.org/10.3892/etm.2021.10016