Etoricoxib in the Prevention of Rat Mammary Carcinogenesis

Abstract

Orendáš P., I. Ahlers, P. Kubatka, E. Ahlersová, B. Bojková, M. Kassayová, L. Friedmanová, J. Kisková, I. Ďatelinka, M. Starostová: Etoricoxib in the Prevention of Rat Mammary Carcinogenesis. Acta Vet. Brno 2007, 76: 613-618. Several experimental studies suggest that non-steroidal antiinflammatory drugs have chemopreventive effects in mammary carcinogenesis. In this study, tumour suppressive effects of a selective inhibitor of cyclooxygenase-2 (COX-2) etoricoxib in the prevention of N-methyl-Nnitrosourea (NMU)-induced mammary carcinogenesis in Sprague-Dawley rats were evaluated. Etoricoxib was administered in the diet, at two concentrations: 1) 0.01 mg/g (ETO 0.001%) and 2) 0.025 mg/g (ETO 0.0025%). Although the chemopreventive effects were not statistically significant, remarkable tumour suppressive effects with the concentration of ETO 0.0025% were recorded. The incidence decreased by 4.31% and tumour frequency per group decreased by 6.67% when compared to the control group. Latency (the period from carcinogen administration to the first tumour appearance) increased by 7.28% in dose-dependent manner. The results of our experiments point to dose-dependent tumour suppressive effects of a higher concentration of etoricoxib (ETO 0.0025%) when compared to the control group. They suggest that higher etoricoxib concentrations may enhance its tumour suppressive effects.

Celecoxib and melatonin in prevention of female rat mammary carcinogenesis

“…In our experiment, celecoxib markedly decreased tumor frequency per group and animal but increased tumor volume. Similar changes in tumor volume were found after etoricoxib application at a dose of 0.025mg/g diet [13]. As opposed to the effect of celecoxib and etoricoxib, administration of rofecoxib in the study by Kubatka et al [12] decreased tumor volume.…”

“…Dietary administered rofecoxib (selective COX-2 inhibitor) in NMUinduced mammary carcinogenesis in female Sprague-Dawley rats markedly decreased tumor incidence and frequency and prolonged latency period by 8 days [12]. The study focused on prevention of NMU-induced mammary carcinogenesis by etoricoxib (selective inhibitor COX-2) administered with diet to female Sprague-Dawley rats reported a tumor suppressive effect at a higher dose (0.025 mg/1 g diet) documented by a slight decrease in tumor incidence, tumor frequency per group, and prolonged latency by 7 days [13].…”

“…Our group proved chemopreventive effects of indomethacin administered in drinking water [9], diclofenac administered in drinking water [10], nimesulide applied subcutaneously [11] and rofecoxib applied in a laboratory diet [12] in mammary carcinogenesis in female Sprague-Dawley rats. Certain anticarcinogenic effect of etoricoxib administered in a laboratory diet [13] was recorded in female Sprague-Dawley rats.…”

Chemopreventive effect of diclofenac on mammary carcinogenesis in Sprague-Dawley rats

“…We found a tumor suppressive effect at a higher dose (0.025 mg g −1 diet) documented by a decrease in tumor incidence, tumor frequency per group and prolonged latency by 7.3% (Orendáš et al 2007). Abou-Issa et al (2001) reported inhibition in DMBA-induced mammary carcinogenesis in female Sprague-Dawley rats by celecoxib (0.25 g kg −1 , 0.50 g kg −1 , 1.00 g kg −1 or 1.50 g kg −1 diet) administered with diet.…”

“…Our group proved the chemopreventive effects of indomethacin administered in drinking water (Môci-ková-Kalická et al 2001), nimesulide applied subcutaneously (Kubatka et al 2002), rofecoxib (Kubatka et al 2003), etoricoxib (Orendáš et al 2007), and celecoxib (Orendáš et al 2009), all administered in the diet to female Sprague-Dawley rats with chemically-induced mammary tumors. Generally, at least 90% of mammary tumors showed malignant features, cribriform carcinoma in situ and invasive adenocarcinomas prevailed; the malignant/benign tumor ratio maintained regardless of oncostatic efficacy (Orendáš et al 2009).…”