Celecoxib potentiates the anticancer effect of cisplatin on vulvar cancer cells independently of cyclooxygenase

Ann N Y Acad Sci. 2009 Aug:1171:635-41. doi: 10.1111/j.1749-6632.2009.04888.x.

Abstract

Cyclooxygenase-2 (COX-2) has been found to be associated with the development and progression of various cancers. Our previous study showed a high expression rate of COX-2 in paraffin-embedded tissue specimens from patients with vulvar cancer. In this study, we evaluated the efficacy of celecoxib, a selective COX-2 inhibitor, as a chemosensitizing agent with cisplatin in vulvar cancer cells A431 and SW962. COX-2 was expressed in both A431 and SW962 vulvar cancer cell lines. COX-1 was expressed in A431 but not in SW962. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide] assay showed that treatment with 30 micromol/L celecoxib had no effect on cell growth in A431 cells for 72 h. However, combined treatment with celecoxib and cisplatin induced a significant reduction in cell growth compared to single treatment with cisplatin. Interestingly, single treatment with celecoxib or cisplatin and combined treatment of 10 micromol/L celecoxib with 10 micromol/L cisplatin increased COX-2 expression. However, the combination of 30 micromol/L celecoxib and 30 micromol/L cisplatin reduced COX-2 expression to the control state. Inhibition of cell growth by celecoxib alone and in combination with cisplatin was independent of the expression level of COX-2 induced by these agents. While treatment with 10 micromol/L celecoxib or 10 micromol/L piroxicam significantly suppressed the activity of COX enzymes, neither agent affected the growth of A431 and SW962 cells at this concentration. Taken together, celecoxib could be used as a chemosensitizing agent in vulva cancer cells; the anticancer activity of celecoxib seemed to be independent of COX.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Blotting, Western
  • Celecoxib
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Cisplatin / pharmacology*
  • Cyclooxygenase 1 / metabolism
  • Cyclooxygenase 2 / metabolism
  • Cyclooxygenase Inhibitors / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Female
  • Humans
  • Piroxicam / pharmacology
  • Prostaglandin-Endoperoxide Synthases / metabolism*
  • Pyrazoles / pharmacology*
  • Sulfonamides / pharmacology*
  • Vulvar Neoplasms / metabolism
  • Vulvar Neoplasms / pathology

Substances

  • Antineoplastic Agents
  • Cyclooxygenase Inhibitors
  • Pyrazoles
  • Sulfonamides
  • Piroxicam
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases
  • Celecoxib
  • Cisplatin