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


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.
Anai
Satoshi
S
Division of Urology, University of Florida, Jacksonville, Florida 32209, USA.
Tanaka
Motoyoshi
M
Shiverick
Kathleen T
KT
Kim
Wanju
W
Takada
Satoshi
S
Boehlein
Susan
S
Goodison
Steve
S
Mizokami
Atushi
A
Rosser
Charles J
CJ
D000230:Adenocarcinoma / Q000201:enzymology / Q000473:pathology / Q000532:radiotherapy; D015153:Blotting, Western; D002318:Cardiovascular Diseases; D000068579:Celecoxib; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004273:DNA, Neoplasm / Q000235:genetics*; D004307:Dose-Response Relationship, Radiation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000473:pathology / Q000532:radiotherapy; D011720:Pyrazoles / Q000494:pharmacology; D011836:Radiation Tolerance / Q000235:genetics*; D013449:Sulfonamides / Q000494:pharmacology
D016861:Cyclooxygenase Inhibitors; D004273:DNA, Neoplasm; D011720:Pyrazoles; D013449:Sulfonamides; D051546:Cyclooxygenase 2; D000068579:Celecoxib