Indomethacin decreases EP2 prostanoid receptor expression in colon cancer cells.
Nonsteroidal anti-inflammatory drugs (NSAIDs) can decrease the risk of colorectal cancer; however, it has not been established if this effect is solely through their ability to inhibit cyclooxygenase (COX). In this study the effects of indomethacin, a potent NSAID and nonselective COX inhibitor, was examined in LS174T human colon cancer cells. These cells were found to express EP2 prostanoid receptors, but not the EP1, EP3 or EP4 subtypes. Pretreatment of LS174T cells with indomethacin produced a complete inhibition of prostaglandin E(2) (PGE(2)) stimulated cyclic AMP (cAMP) formation in a dose dependent manner with an IC(50) of 21 microM. Interestingly, the inhibition of PGE(2)-stimulated cAMP formation by indomethacin was accompanied by a decrease in EP2 mRNA expression and by a decrease in the whole cell specific binding of [(3)H]PGE(2). Thus, treatment of LS174T cells with indomethacin causes a down regulation of EP2 prostanoid receptors expression that may be independent of COX inhibition.
Fujino
Hiromichi
H
Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, Japan. fujino@p.chiba-u.ac.jp
Chen
Xiao-bo
XB
Regan
John W
JW
Murayama
Toshihiko
T
D045744:Cell Line, Tumor; D005576:Colforsin / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism*; D000242:Cyclic AMP / Q000096:biosynthesis; D015232:Dinoprostone / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D018078:Receptors, Prostaglandin E / Q000235:genetics / Q000378:metabolism*; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058308:Receptors, Prostaglandin E, EP3 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype
C545644:PTGER2 protein, human; C545647:PTGER3 protein, human; C545650:PTGER4 protein, human; D012333:RNA, Messenger; D018078:Receptors, Prostaglandin E; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058308:Receptors, Prostaglandin E, EP3 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D005576:Colforsin; D000242:Cyclic AMP; D015232:Dinoprostone; D007213:Indomethacin