Selective cyclooxygenase-2 inhibitors inhibit growth and induce apoptosis of bladder cancer

Oncol Rep. 2006 Feb;15(2):471-7.


Selective COX-2 inhibitors such as celecoxib and NS-398 are being evaluated as chemopreventive and therapeutic agents for bladder and other cancers. We investigated the effects of these nonsteroidal anti-inflammatory agents on a panel of bladder cancer cell lines, and assessed their effects on anchorage-dependent and -independent growth, cell cycle, apoptosis and morphology. The human bladder cancer cell lines UM-UC-1, -3, and -6 were assayed for COX-2 expression by Western analysis using a monoclonal antibody to COX-2. UM-UC-1, -3, and -6 cells were grown in the presence of increasing concentrations of NS-398 and celecoxib, and cell growth was quantitated over 7 days by crystal violet elution. The cell lines were treated with NS-398 and celecoxib for 48 h and analyzed by flow cytometry with propidium iodide staining and Br-dUTP staining for apoptosis. Anchorage-independent growth was assessed using an agarose growth assay. Western analysis demonstrated that COX-2 expression in UM-UC-1, -6, and -3 was high, low, and undetectable, respectively. NS-398 and celecoxib produced dose-dependent growth inhibition of UM-UC-1 and -6. Both NS-398 and celecoxib also inhibited anchorage-dependent and -independent growth of UM-UC-3 in a dose-dependent fashion, despite the low basal expression of COX-2 in this cell line. Cell cycle analyses of UM-UC-1 and -6 revealed a 50% reduction in S-phase in the presence of 100 microM NS-398 whereas a smaller reduction in S-phase was noted in UM-UC-3 cells. Furthermore, treatment with 100 microM celecoxib resulted in significant apoptosis in all three cell lines, which was associated with downregulation of Bcl-2. COX-2 selective inhibitors NS-398 and celecoxib produced dose-dependent growth inhibition of bladder cancer cells associated with a significant reduction in S-phase. Induction of apoptosis in all three cell lines by celecoxib was associated with downregulation of Bcl-2. These changes occur independently of COX-2 expression levels suggesting the presence of a COX-2 independent pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Blotting, Western
  • Carcinoma, Transitional Cell / drug therapy*
  • Celecoxib
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Cyclooxygenase 2 / drug effects
  • Cyclooxygenase 2 / metabolism
  • Cyclooxygenase 2 Inhibitors / pharmacology*
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Flow Cytometry
  • Humans
  • Nitrobenzenes / pharmacology
  • Proto-Oncogene Proteins c-bcl-2 / drug effects
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Pyrazoles / pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sulfonamides / pharmacology
  • Urinary Bladder Neoplasms / drug therapy*


  • Cyclooxygenase 2 Inhibitors
  • Nitrobenzenes
  • Proto-Oncogene Proteins c-bcl-2
  • Pyrazoles
  • Sulfonamides
  • N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
  • Cyclooxygenase 2
  • Celecoxib