Resistance of prostate cancer cell lines to COX-2 inhibitor treatment.
Targeting of cyclooxygenase-2 (COX-2) for cancer chemoprevention is well supported for several tumor types, most notably colon cancer. In contrast, the data for its role in prostate cancer carcinogenesis are correlative only. Thus, we compared the COX-2 expression, activity, and effects of inhibition in prostate cancer cells on COX-2-dependent colon cancer cells. COX-2 levels in benign and malignant human prostate tissue were determined by immunohistochemistry. Compared to colon cancer cells, prostate cancer cells expressed lower levels of COX-2, produced less PGE2, and were resistant to selective COX-2 inhibition. Examination of benign prostatic epithelium from prostatectomy samples demonstrated rare foci of COX-2. Whereas, human prostate cancer sections were uniformly negative for COX-2. In conclusion, these studies indicate the lack of a putative role for COX-2 in prostate cancer development. Direct evidence for the involvement of COX-2 in prostate cancer carcinogenesis is desperately needed.
Wagner
Matthew
M
Division of Urology and Renal Transplantation, Oregon Health and Science University, Oregon Cancer Institute, Portland, OR, USA.
Loos
James
J
Weksler
Nicole
N
Gantner
Marin
M
Corless
Christopher L
CL
Barry
John M
JM
Beer
Tomasz M
TM
Garzotto
Mark
M
D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000096:biosynthesis; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins; D009578:Nitrobenzenes / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D013449:Sulfonamides / Q000494:pharmacology
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D008565:Membrane Proteins; D009578:Nitrobenzenes; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone