Cyclooxygenase-2 promotes ovarian cancer cell migration and cisplatin resistance via regulating epithelial mesenchymal transition

J Zhejiang Univ Sci B. 2020;21(4):315-326. doi: 10.1631/jzus.B1900445.

Abstract

Objective: Drug-resistance and metastasis are major reasons for the high mortality of ovarian cancer (OC) patients. Cyclooxygenase-2 (COX-2) plays a critical role in OC development. This study was designed to evaluate the effects of COX-2 on migration and cisplatin (cis-dichloro diammine platinum, CDDP) resistance of OC cells and explore its related mechanisms.

Methods: Cell counting kit-8 (CCK-8) assay was used to detect the cytotoxicity effects of celecoxib (CXB) and CDDP on SKOV3 and ES2 cells. The effect of COX-2 on migration was evaluated via the healing test. Western blot and real-time quantitative polymerase chain reaction (qPCR) were used to analyze E-cadherin, vimentin, Snail, and Slug levels.

Results: COX-2 promoted drug-resistance and cell migration. CXB inhibited these effects. The combination of CDDP and CXB increased tumor cell sensitivity, reduced the amount of CDDP required, and shortened treatment administration time. COX-2 upregulation increased the expression of Snail and Slug, resulting in E-cadherin expression downregulation and vimentin upregulation.

Conclusions: COX-2 promotes cancer cell migration and CDDP resistance and may serve as a potential target for curing OC.

Keywords: Ovarian cancer (OC); Cyclooxygenase-2 (COX-2); Drug resistance; Migration; Epithelial-mesenchymal transition (EMT).

MeSH terms

  • Celecoxib / pharmacology
  • Cell Line, Tumor
  • Cell Movement
  • Cisplatin / pharmacology*
  • Cyclooxygenase 2 / physiology*
  • Drug Resistance, Neoplasm
  • Epithelial-Mesenchymal Transition*
  • Female
  • Humans
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / pathology*
  • Polymerase Chain Reaction

Substances

  • Cyclooxygenase 2
  • Celecoxib
  • Cisplatin