Increased Expression of Cyclooxygenase-2 Correlates With Resistance to Radiation in Human Prostate Adenocarcinoma Cells

Satoshi Anai, Motoyoshi Tanaka, Kathleen T. Shiverick, Wanju Kim, Satoshi Takada, Susan Boehlein, Steven Goodison, Atushi Mizokami, Charles J. Rosser

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

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 μM 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.

Original languageEnglish (US)
Pages (from-to)1913-1917
Number of pages5
JournalJournal of Urology
Volume177
Issue number5
DOIs
StatePublished - May 1 2007
Externally publishedYes

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Keywords

  • carbonic anhydrases
  • celecoxib
  • cyclooxygenase-2
  • prostate
  • radiotherapy

ASJC Scopus subject areas

  • Urology

Cite this

Anai, S., Tanaka, M., Shiverick, K. T., Kim, W., Takada, S., Boehlein, S., Goodison, S., Mizokami, A., & Rosser, C. J. (2007). Increased Expression of Cyclooxygenase-2 Correlates With Resistance to Radiation in Human Prostate Adenocarcinoma Cells. Journal of Urology, 177(5), 1913-1917. https://doi.org/10.1016/j.juro.2007.01.019