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Gastroenterology Research and Practice
Volume 2010 (2010), Article ID 640797, 14 pages
http://dx.doi.org/10.1155/2010/640797
Research Article

Rosuvastatin Counteracts Vessel Arterialisation and Sinusoid Capillarisation, Reduces Tumour Growth, and Prolongs Survival in Murine Hepatocellular Carcinoma

1Institut des Vaisseaux et du Sang, Hôpitlal Lariboisière, 2 Rue Ambroise Paré, 75010 Paris, France
2“Angiogenèse et Recherche Translationnelle” INSERM U 965 “Equipe labellisée Ligue 2009”, HÔpital Lariboisière, 2 Rue Ambroise Paré, 75010 Paris, France
3Université Paris 7 Denis Diderot, 10 Avenue de Verdun, 75010 Paris, France
4Laboratoire M.E.R.C.I, Université de Rouen, 22 Boulevard Gambetta, 76183 Rouen Cedx, France
5HÔpital Lariboisière, 2 Rue Ambroise Paré, 75010 Paris, France
6Paris Cardiovascular Research Center, INSERM U970, HÔpital Européen Georges Pompidou, 20 Rue Leblanc, 75015 Paris, France
7HÔpital Européen Georges Pompidou, 20 Rue Leblanc, 75015 Paris, France
8Université Descartes-Paris 5, 12 Rue de l’École de Médecine, 75006 Paris, France

Received 29 September 2010; Accepted 28 December 2010

Academic Editor: Fabio Marra

Copyright © 2010 Annemilaï Tijeras-Raballand et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background and Aims. An arterial blood supply and phenotypic changes of the sinusoids characterise the liver vasculature in human hepatocellular carcinoma (HCC). We investigated the effects of rosuvastatin on liver vessel anomalies, tumour growth and survival in HCC. Methods. We treated transgenic mice developing HCC, characterized by vessel anomalies similar to those of human HCC, with rosuvastatin. Results. In the rosuvastatin group, the survival time was longer , and liver weight and nodule surface were reduced. Rosuvastatin decreased the number of smooth muscle actin-positive arteries and prevented the sinusoid anomalies, with decreased laminin expression , activated hepatic stellate cells , and active Notch4 expression. Furthermore, rosuvastatin inhibited endothelial cell but not tumour hepatocyte functions. Conclusions. Rosuvastatin reduced the vessel anomalies and tumour growth and prolonged survival in HCC. These results represent new mechanisms of the effects of statin on tumour angiogenesis and a potential target therapy in HCC.