The molecular mechanisms of celecoxib in tumor development

Medicine (Baltimore). 2020 Oct 2;99(40):e22544. doi: 10.1097/MD.0000000000022544.

Abstract

Background: Clinical studies have shown that celecoxib can significantly inhibit the development of tumors, and basic experiments and in vitro experiments also provide a certain basis, but it is not clear how celecoxib inhibits tumor development in detail.

Methods: A literature search of all major academic databases was conducted (PubMed, China National Knowledge Internet (CNKI), Wan-fang, China Science and Technology Journal Database (VIP), including the main research on the mechanisms of celecoxib on tumors.

Results: Celecoxib can intervene in tumor development and reduce the formation of drug resistance through multiple molecular mechanisms.

Conclusion: Celecoxib mainly regulates the proliferation, migration, and invasion of tumor cells by inhibiting the cyclooxygenases-2/prostaglandin E2 signal axis and thereby inhibiting the phosphorylation of nuclear factor-κ-gene binding, Akt, signal transducer and activator of transcription and the expression of matrix metalloproteinase 2 and matrix metalloproteinase 9. Meanwhile, it was found that celecoxib could promote the apoptosis of tumor cells by enhancing mitochondrial oxidation, activating mitochondrial apoptosis process, promoting endoplasmic reticulum stress process, and autophagy. Celecoxib can also reduce the occurrence of drug resistance by increasing the sensitivity of cancer cells to chemotherapy drugs.

MeSH terms

  • Apoptosis / drug effects
  • Autophagy / drug effects
  • Celecoxib / adverse effects
  • Celecoxib / pharmacology*
  • Celecoxib / therapeutic use
  • Cell Proliferation / drug effects
  • Cyclooxygenase 2 Inhibitors / adverse effects
  • Cyclooxygenase 2 Inhibitors / pharmacology*
  • Cyclooxygenase 2 Inhibitors / therapeutic use
  • Dinoprostone / metabolism
  • Drug Resistance, Neoplasm / drug effects*
  • Endoplasmic Reticulum Stress / drug effects
  • Humans
  • Matrix Metalloproteinase 2 / drug effects
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / drug effects
  • Matrix Metalloproteinase 9 / metabolism
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Neoplasms / drug therapy*
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-akt / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction / drug effects

Substances

  • Cyclooxygenase 2 Inhibitors
  • Proto-Oncogene Proteins c-akt
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • Celecoxib
  • Dinoprostone