The selective cyclooxygenase-2 inhibitor nimesulide induces apoptosis in pancreatic cancer cells independent of COX-2

Pancreas. 2003 Jan;26(1):33-41. doi: 10.1097/00006676-200301000-00007.


Introduction: Selective cyclooxygenase-2 (COX-2) inhibition reduces the growth of many cancer cell lines, and this effect may be mediated through induction of apoptosis. This study was designed to investigate the effects of the COX-2 inhibitor nimesulide on the growth of human pancreatic cancer cells.

Methodology: Reverse transcriptase-polymerase chain reaction analysis, northern blotting, and immunoblotting were used to demonstrate COX-2 mRNA and protein in two pancreatic cancer cell lines: BxPC-3 and MIA PaCa-2. The effect of nimesulide on cell growth was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and cell count. Apoptosis was determined by FACS analysis, DNA laddering, and assessment of the floating cell/attached cell ratio. Caspase-3 activation was evaluated by measuring caspase-3 cellular activity and by determining the effects of two caspase inhibitors on cell viability.

Results: COX-2 mRNA was detected in both cell lines. Immunoblotting confirmed COX-2 protein expression in only the BxPC-3 cell line. Nimesulide decreased cell viability and inhibited cell growth in both cell lines. Incubation with 100 micromol/L nimesulide increased the fraction of apoptotic cells and the floating cell/attached cell ratio in both cell lines. DNA laddering was observed after incubation with nimesulide for 96 hours. There was no increase in caspase-3 activity within 96 hours.

Conclusion: The selective COX-2 inhibitor nimesulide is antimitogenic in pancreatic cancer cells, which is independent of COX-2 expression. This effect in part is mediated by the induction of apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis*
  • Caspase 3
  • Caspases / metabolism
  • Cell Division / drug effects
  • Cell Survival / drug effects
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors / pharmacology*
  • Humans
  • Isoenzymes / antagonists & inhibitors*
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Membrane Proteins
  • Pancreatic Neoplasms / enzymology*
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / pathology
  • Prostaglandin-Endoperoxide Synthases / genetics
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • RNA, Messenger / biosynthesis
  • Sulfonamides / pharmacology*
  • Tumor Cells, Cultured


  • Antineoplastic Agents
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Isoenzymes
  • Membrane Proteins
  • RNA, Messenger
  • Sulfonamides
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • CASP3 protein, human
  • Caspase 3
  • Caspases
  • nimesulide