Influencia de la inhibición selectiva de la ciclo-osigenasa 2 en la prevención de tumores colorrectales farmacologicamente inducidos.

Abstract

Objectives To investigate the effect of the selective inhibition of the cyclooxygenase-2 (COX-2) in the prevention of colonic tumors and in the activity COX-2 expressed in the tumoral tissue. Material and methods Experimental study with 35 male Sprague-Dawley rats, divided into four groups: a) control group (n=5) without experimental manipulation, b) pharmacological carcinogenesis (n=10) with 1,2-dimethyhydrazine dihydrocloride (1,2-DMH) at a weekly dose of 25 mg/Kg during 18 weeks (Group DMH), c) carcinogenesis and nonselective inhibition of COX (n=10) (Group DMH + AAS) with administration of acetylsalicylic acid (ASA) at dose of 30 mg/Kg/day during 18 weeks at the same time of carcinogenesis, and d) carcinogenesis and selective inhibition of COX-2 (n=10) (Group DMH + RFC), with administration of rofecoxib (RFC) at dose of 3 mg/Kg/day during 18 weeks at the same time of carcinogenesis. The induced colonic tumors were analyzed with microscopic and immunohistochemical studies in 20th week of the beginning of the manipulation. Results A total of 57 tumors have been obtained, 27 adenomas and 30 adenocarcinomas, without differences between the groups. The tumors of the group DMH + RFC display significantly better results in relation to the tumors of the group DMH with respect to total microscopic tumor surface area, to malignant microscopic tumor percentage and to total microscopic tumor percentage. Moreover, significant reductions of the expression of activity COX-2 are appraised in the tumoral tissue of the adenomas, in the expression of activity COX-2 the tumoral and peritumoral tissue of the adenomas and in expression COX-2 in the tumoral tissue of adenocarcinomas in favour of the tumors of the group DMH + RFC as opposed to those of group DMH. There are not significant differences between the tumors of the group DMH + AAS as opposed to those of the other groups neither in the amount of induced tumor nor in the expression of COX-2 activity in the tumoral tissue. Conclusions The selective inhibition of COX-2 activity produces a significant diminution of the amount of induced tumor through a diminution of the expression of COX-2 activity in the tumoral tissue.