Celecoxib inhibits the epithelial-to-mesenchymal transition in bladder cancer via the miRNA-145/TGFBR2/Smad3 axis

Int J Mol Med. 2019 Aug;44(2):683-693. doi: 10.3892/ijmm.2019.4241. Epub 2019 Jun 12.

Abstract

Celecoxib, a selective cyclooxygenase‑2 inhibitor, has chemo‑preventive activity against different cancer types, including bladder cancer (BC). However, the mechanisms by which celecoxib exerts its cancer preventative effects have yet to be completely understood. In the present study, the effect of celecoxib on the epithelial‑to‑mesenchymal transition (EMT) of BC cells and its potential molecular mechanisms were investigated. The results of the present study demonstrated that celecoxib inhibited the proliferation, migration, invasion and EMT of BC cells. Further investigation of the underlying mechanism revealed that celecoxib inhibited EMT by upregulating microRNA (miR)‑145 and downregulating the expression of transforming growth factor β receptor 2 and SMAD family member 3. Furthermore, the combination of celecoxib with miR‑145 mimics demonstrated an additive migration and invasion‑inhibitory effect in BC cell lines.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Celecoxib / pharmacology*
  • Cell Line
  • Cell Line, Tumor
  • Cyclooxygenase 2 Inhibitors / pharmacology*
  • Epithelial-Mesenchymal Transition / drug effects*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / prevention & control
  • Receptor, Transforming Growth Factor-beta Type II / genetics
  • Smad3 Protein / genetics
  • Urinary Bladder Neoplasms / drug therapy*
  • Urinary Bladder Neoplasms / genetics

Substances

  • Antineoplastic Agents
  • Cyclooxygenase 2 Inhibitors
  • MIRN145 microRNA, human
  • MicroRNAs
  • SMAD3 protein, human
  • Smad3 Protein
  • Receptor, Transforming Growth Factor-beta Type II
  • Celecoxib