Simvastatin impairs murine melanoma growth

Lipids in Health and Disease

Research

Durvanei A Maria¹  Francisco E Barros²  Primavera Borelli²  Sergio P Bydlowski³  Milton S Bohatch⁴  Karen A Oliveira⁴  Michel F Otuki⁴  Daniel Fernandes⁴  Giovani M Favero⁵ 

[1] Biochemistry and Biophisics Laboratories, Butantan Institute, São Paulo, Brazil;Experimental Hematology Laboratory, Faculty of Pharmaceutical Sciences, Department of Clinical and Toxicological Analyses, University of São Paulo, São Paulo, Brazil;Laboratory of Genetics and Molecular Hematology, Department of Hematology (LIM 31), University of São Paulo Medical School, São Paulo, Brazil;State University of Ponta Grossa, Biological and Health Science Multidisciplinary Laboratory, Ponta Grossa, Brazil;State University of Ponta Grossa, Biological and Health Science Multidisciplinary Laboratory, Ponta Grossa, Brazil;Laboratory of Genetics and Molecular Hematology, Department of Hematology (LIM 31), University of São Paulo Medical School, São Paulo, Brazil;

关键词: Melanoma;    Melanoma Cell;    Simvastatin;    Gamma Glutamyl Transferase;    Mouse Melanoma;   

DOI  :  10.1186/1476-511X-9-142

 received in 2010-12-02, accepted in 2010-12-16,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundStatins induces cell cycle arrest, apoptosis, reduction of angiogenic factors, inhibition of the endothelial growth factor, impairing tissue adhesion and attenuation of the resistance mechanisms. The aim of this study was evaluate the anti-tumoral activity of simvastatin in a B16F10 melanoma-mouse model.MethodsMelanoma cells were treated with different concentrations of simvastatin and assessed by viability methods. Melanoma cells (5 × 104) were implanted in two month old C57Bl6/J mice. Around 7 days after cells injection, the oral treatments were started with simvastatin (5 mg/kg/day, p.o.). Tumor size, hematological and biochemical analyses were evaluated.ResultsSimvastatin at a concentration of 0.8 μM, 1.2 μM and 1.6 μM had toxic effect. Concentration of 1.6 μM induced a massive death in the first 24 h of incubation. Simvastatin at 0.8 μM induces early cell cycle arrest in G0/G1, followed by increase of hypodiploidy. Tumor size were evaluated and the difference of treated group and control, after ten days, demonstrates that simvastatin inhibited the tumor expansion in 68%.ConclusionSimvastatin at 1.6 μM, presented cytototoxicity after 72 h of treatment, with an intense death. In vivo, simvastatin being potentially useful as an antiproliferative drug, with an impairment of growth after ten days.

【 授权许可】

CC BY   
© Favero et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.