Requirement of cyclooxygenase-2 expression and prostaglandins for human prostate cancer cell invasion.
The PC-3 Low Invasive cells and the PC-3 High Invasive cells were used to investigate the correlation of the COX-2 expression and its arachidonic acid metabolites, prostaglandins, with their invasiveness through Matrigel using a Boyden chamber assay. The COX-2 expression in PC-3 High Invasive cells was approximately 3-fold higher than in PC-3 Low Invasive cells while the COX-1 expression was similar in both cell sublines. When incubated with arachidonic acid, PGE2 was the major prostaglandin produced by these cells. PC-3 High Invasive cells produced PGE2 approximately 2.5-fold higher than PC-3 Low Invasive cells. PGD2 was the second most abundant prostaglandin produced by these cells. Both indomethacin (a nonspecific COX inhibitor) and NS-398 (a specific COX-2 inhibitor) inhibited the production of prostaglandins and the cell invasion. PGE2 alone did not induce the cell invasion of PC-3 Low Invasive cells. However, PGE2 reversed the inhibition of cell invasion by NS-398 and enhanced the cell invasion of the PC-3 High Invasive cells. In contrast, PGD2 slightly inhibited the cell invasion. These results suggest that in the PC-3 Low Invasive cells, COX-2-derived PGE2 may not be sufficient to induce cell invasion while in the PC-3 High Invasive cells, PGE2 may be sufficient to act as an enhancer for the cell invasion. Further, PGD2 may represent a weak inhibitor and counteracts the effect of PGE2 in the cell invasion.
Nithipatikom
Kasem
K
Department of Pharmacology & Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA. kasemn@mcw.edu
Isbell
Marilyn A
MA
Lindholm
Paul F
PF
Kajdacsy-Balla
Andre
A
Kaul
Sushma
S
Campell
William B
WB
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D016718:Arachidonic Acid / Q000378:metabolism; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015237:Dinoprost / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D009361:Neoplasm Invasiveness; D009578:Nitrobenzenes / Q000494:pharmacology; D015230:Prostaglandin D2 / Q000378:metabolism / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D013449:Sulfonamides / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D009578:Nitrobenzenes; D011453:Prostaglandins; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D016718:Arachidonic Acid; D015121:6-Ketoprostaglandin F1 alpha; D015237:Dinoprost; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D015230:Prostaglandin D2; D007213:Indomethacin