Chemoprevention of mammary carcinogenesis in female rats by rofecoxib.
Epidemiological and experimental studies indicate that non-steroidal anti-inflammatory drugs play role in the prevention of human neoplasia including mammary gland cancer. In this study, tumour suppressive effects of a selective inhibitor of cyclooxygenase-2 (COX-2) rofecoxib in the prevention of N-methyl-N-nitrosourea (NMU)-induced mammary carcinogenesis in female Sprague-Dawley rats were evaluated. Rofecoxib was dietary administered in two concentrations-0.01 mg/1 g (ROFE 0.001%), or 0.05 mg/1 g (ROFE 0.005%). Rofecoxib decreased the incidence by 40% (ROFE 0.001%) and by 42.5% (ROFE 0.005%) (P=0.043) when compared to the control group. Similarly, tumour frequency and tumour volume decreased depending on an increasing rofecoxib dose by 18.5 or 40% (tumour frequency) and by 35 or 43% (tumour volume). Rofecoxib shifted the rate of fibroadenomas from 15% (control group) to 32% (ROFE 0.001%), or 38% (ROFE 0.005%), respectively. The present study points to pronounced dose-dependent tumour suppressive effects of rofecoxib in mammary carcinogenesis.
Kubatka
Peter
P
Department of Animal Physiology, Institute of Biological and Ecological Sciences, Faculty of Science, P.J. Safárik University, Moyzesova 11, 04167 Kosice, Slovak Republic.
Ahlers
Ivan
I
Ahlersová
Eva
E
Adámeková
Eva
E
Luk
Pauline
P
Bojková
Bianka
B
Marková
Martina
M
D000477:Alkylating Agents / Q000633:toxicity; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use*; D004032:Diet; D004305:Dose-Response Relationship, Drug; D005260:Female; D007783:Lactones / Q000008:administration & dosage / Q000627:therapeutic use*; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008770:Methylnitrosourea / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D013450:Sulfones
D000477:Alkylating Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D007783:Lactones; D013450:Sulfones; C116926:rofecoxib; D008770:Methylnitrosourea