Effects of cyclooxygenase-2 inhibitor NS-398 on APC and c-myc expression in rat colon carcinogenesis induced by azoxymethane.
BACKGROUND
Nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to protect against the development of colon cancer; however, the mechanism(s) by which NSAIDs exert their effects is still unclear. The aim of this study was to examine the effects of NSAIDs on the expression of the tumor suppressor APC gene and the c-myc oncogene in the colons of rats treated with a colon-specific carcinogen, azoxymethane (AOM).


METHODS
Gene expression levels were estimated by a reverse transcription (RT)-competitive polymerase chain reaction (PCR) method.


RESULTS
The group of rats simultaneously administered AOM and NS-398, a cyclooxygenase (COX)-2 inhibitor, showed a significant reduction in the number of preneoplastic lesions of colon cancer compared with that in the group of rats treated with AOM alone. Furthermore, the APC expression level in the group of rats treated with both AOM and NS-398 was significantly greater than that in the group of rats treated with AOM alone; this result for APC gene expression was reconfirmed by the immunohistochemical staining of APC protein. In addition, c-myc mRNA expression was clearly decreased in the group of rats treated with both AOM and NS-398 compared with the level in the group of rats treated with AOM alone.


CONCLUSIONS
Our data thus indicate that NS-398 causes an increase in APC expression and a decrease in c-myc expression.
Kishimoto
Yosuke
Y
Department of Clinical Pharmacology, Faculty of Medicine, Tottori University, Yonago, Japan.
Yashima
Kazuo
K
Morisawa
Tsuyoshi
T
Shiota
Goshi
G
Kawasaki
Hironaka
H
Hasegawa
Junichi
J
D000818:Animals; D001397:Azoxymethane; D002273:Carcinogens; D002277:Carcinoma / Q000139:chemically induced / Q000188:drug therapy*; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000188:drug therapy*; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D017491:Genes, APC / Q000187:drug effects*; D016259:Genes, myc / Q000187:drug effects; D007150:Immunohistochemistry; D008297:Male; D023421:Models, Animal; D009578:Nitrobenzenes / Q000627:therapeutic use*; D051381:Rats; D011916:Rats, Inbred F344; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013449:Sulfonamides / Q000627:therapeutic use*
D002273:Carcinogens; D016861:Cyclooxygenase Inhibitors; D009578:Nitrobenzenes; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D001397:Azoxymethane