AMBIVALENT EFFECTS OF ATORVASTATIN ON ANGIOGENESIS, EPIDERMAL CELL PROLIFERATION AND TUMORGENESIS IN ANIMAL MODELS

摘要: Background: A growing body of preclinical data indicates that statins may possess antineoplastic properties; however, some studies have raised the possibility also carcinogenic potential. Methods: An air pouch model was used for angiogenesis. Single or multiple applications croton oil on back Swiss albino mice with without initiation by dimethylbenz(a)antheracene (DMBA) were to evaluate skin tumorgenesis, ultrastructural and histological alterations. Results: Atorvastatin (orally, 10 mg/kg/day) produced a significant (P<0.05) reduction in Concurrent administration mevalonate reversed antiangiogenic effect atorvastatin. However, local injection atorvastatin (200 µg) into pouches induced (P<0.5) increase angiogenesis not co-administration mevalonate. The disturbance cell polarity, inflammatory response, thickness epidermal layer, mitotic index inhibited markedly dose-dependently (P<0.001) pre-treatment In spite strong anti-inflammatory anti-proliferative effects proliferation, it identified same doses DMBA-initiated oil-promoted tumorgenesis increased incidence tumors their conversion malignant carcinoma. Conclusion: reasons these discrepancies remain unclear, could be related ambivalent specific differences experimental conditions. It is suggested pro-angiogenic drug, which responsible promotion tumors, independent 3-hydroxy-3-methyl-glutaryl-coenzyme reductase inhibition can mediated directly Iran. Biomed. J. 16 (2): 59-67, 2012