Cyclooxygenase-2 inhibition in colon experimental carcinogenesis.
BACKGROUND
An overexpression of cyclooxygenase-2 (COX-2) has been seen in colon tumors; therefore, COX-2 specific inhibitors may be used as preventive agents. The aim of this study was to investigate the effect of both selective and non-selective COX-2 inhibitors on the incidence of colonic tumors in a model of chemical carcinogenesis in the rat.


METHODS
Experimental study with 65 male Sprague-Dawley rats randomly assigned to one of four groups: (a) control (n = 20), with chemical carcinogenesis using 1-2 dimethylhydrazine (1-2 DMH); (b) acetylsalicylic acid (ASA) (n = 15), with chemical carcinogenesis and the addition of ASA at 30 mg/kg; (c) low-dose rofecoxib (n = 15), with chemical carcinogenesis and the addition of rofecoxib at a dose of 1.2 mg/kg; (d) high-dose rofecoxib (n = 15), with carcinogenesis and the addition of rofecoxib at 3 mg/kg. Carcinogenic induction was performed with 1-2 DMH at a weekly dose of 25 mg/kg for 18 weeks. The main parameter evaluated was percentage of neoplastic colonic tissue, which relates tumor surface area to colon surface area.


RESULTS
Rofecoxib at a dose of 3 mg/kg significantly reduced chemical colon carcinogenesis in rats (p < 0.01). Rofecoxib in lower doses had the same effect on adenomas (p < 0.05) with no effect on adenocarcinomas. Rofecoxib reduced COX-2 expression in tumoral tissue from adenomas and adenocarcinomas (p < 0.01).


CONCLUSIONS
Rofecoxib prevents chemical colon carcinogenesis in the rat, with a reduction of tumoral colonic percentage in adenocarcinomas and tumoral COX-2 expression.
Noguera Aguilar
J F
JF
Unit of Surgery, Hospital Son Llàtzer, Baleares. jnoguera@hsll.es
Amengual Antich
I
I
Plaza Martínez
A
A
Ibarra de la Rosa
J
J
Tortajada Collado
C
C
Gamundí Gamundí
A
A
Pujol Tugores
J J
JJ
D019813:1,2-Dimethylhydrazine; D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D004195:Disease Models, Animal; D007783:Lactones / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013450:Sulfones / Q000494:pharmacology
D052246:Cyclooxygenase 2 Inhibitors; D007783:Lactones; D013450:Sulfones; C116926:rofecoxib; D051546:Cyclooxygenase 2; D019813:1,2-Dimethylhydrazine; D001241:Aspirin