Increased expression of cyclooxygenase-2 correlates with resistance to radiation in human prostate adenocarcinoma cells

J Urol. 2007 May;177(5):1913-7. doi: 10.1016/j.juro.2007.01.019.


Purpose: Cyclooxygenase-2 functions as a survival factor by protecting cells from apoptosis. We analyzed cyclooxygenase-2 expression in LNCaP-COX-2 and LNCaP-Neo cell lines treated with irradiation.

Materials and methods: LNCaP-COX-2 and LNCaP-Neo cells were treated with 0 to 500 microM celecoxib and a dose response curve was generated. A clonogenic assay was performed in which cells were subjected to irradiation (0 to 6 Gy) with or without celecoxib. Cyclooxygenase-2 protein and other relevant proteins were measured by immunohistochemistry Western blot analysis after irradiation and celecoxib treatment.

Results: The 2 studied cell lines experienced cytotoxic effects of celecoxib in a dose related manner. Clonogenic assays demonstrated that LNCaP-COX-2 cells were significantly more resistant to radiation therapy than LNCaP-Neo cells. Furthermore, the addition of celecoxib sensitized LNCaP-Neo and LNCaP-COX-2 cells to the cytocidal effects of radiation. Moreover, cyclooxygenase-2 over expression was associated with the over expression of pAkt and carbonic anhydrase. In this cell line irradiation alone was associated with increased expression of cyclooxygenase-2 and carbonic anhydrase. Combination therapy with irradiation and celecoxib down-regulated cyclooxygenase-2, pAKT and carbonic anhydrase. LNCaP-Neo cells expressed carbonic anhydrase and pAkt. Irradiation of these cells increased carbonic anhydrase and pAkt expression. Combination therapy with irradiation and celecoxib down-regulated carbonic anhydrase and pAkt.

Conclusions: Cyclooxygenase-2 expression is also associated with pAkt and carbonic anhydrase expression. Down-regulation of cyclooxygenase-2 by celecoxib is associated with decreased expression of cyclooxygenase-2, pAkt and carbonic anhydrase, and eventual radiation sensitization, which is a phenomenon that may have clinical usefulness.

MeSH terms

  • Adenocarcinoma* / enzymology
  • Adenocarcinoma* / pathology
  • Adenocarcinoma* / radiotherapy
  • Blotting, Western
  • Cardiovascular Diseases
  • Celecoxib
  • Cell Line, Tumor
  • Cell Survival / radiation effects
  • Cyclooxygenase 2 / biosynthesis
  • Cyclooxygenase 2 / drug effects
  • Cyclooxygenase 2 / genetics*
  • Cyclooxygenase Inhibitors / pharmacology
  • DNA, Neoplasm / genetics*
  • Dose-Response Relationship, Radiation
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunohistochemistry
  • Male
  • Prostatic Neoplasms* / enzymology
  • Prostatic Neoplasms* / pathology
  • Prostatic Neoplasms* / radiotherapy
  • Pyrazoles / pharmacology
  • Radiation Tolerance / genetics*
  • Sulfonamides / pharmacology


  • Cyclooxygenase Inhibitors
  • DNA, Neoplasm
  • Pyrazoles
  • Sulfonamides
  • Cyclooxygenase 2
  • Celecoxib