alexa Atorvastatin-Induced Inhibition of Human Melanoma In Vi
ISSN: 2471-9552

Immunotherapy: Open Access
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Research Article

Atorvastatin-Induced Inhibition of Human Melanoma In Vivo Development

Sarrabayrouse Guillaume3#, Teiti Iotefa1,2#, Filali Liza1,2, Maisongrosse Véronique2, Rochaix Philippe2,4 and Tilkin-Mariamé Anne-Françoise5*

1Unité INSERM UMR 1037, CRCT, Toulouse F-31052, France

2Université Paul Sabatier, Toulouse F-31062, France

3Digestive System Research Unit, Vall d'Hebron Research Institute, Passeig Vall d'Hebron 119-129, Barcelona 08035, Spain

4Institut Universitaire du Cancer, Toulouse F-31037, France

5Pathophysiology of the Intestinal Epithelium Institut de Recherche en Santé Digestive (IRSD) INSERM U.1220, INRA, ENVT, UT3, Toulouse F-31024, France

#Co-first authors

*Corresponding Author:
Tilkin-Mariamé Anne-Françoise
INSERM U1037 - Université Toulouse 3 - ERL5294 CNRS
2 avenue Hubert Curien
31037 Toulouse - France
Tel: 33 5 82 74 16
E-mail: [email protected]

Received date: December 23, 2015 Accepted date: January 30, 2016 Published date: February 10, 2016

Citation: Iotefa T, Guillaume S, Liza F, Véronique M, Philippe R, et al. (2016) Atorvastatin-Induced Inhibition of Human Melanoma in vivo Development. Immunother Open Acc 2:111. doi:10.4172/2471-9552.1000111

Copyright: © 2016 Iotefa T, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

 

Abstract

Statins, 3-hydroxy 3-methylglutaryl CoA (HMG-CoA) reductase inhibitors, are pleiotropic pharmacological inhibitors, which block the mevalonate synthesis pathway. They are widely used as hypocholesterolemic agents and have shown protective effects against cancers. Our previous data showed that statin treatment induced MHC class I chain-related protein A (MICA) membrane overexpression in human melanoma cells, which increased their sensitivity to NK cell cytotoxicity and thus the inhibition of tumor development. MICA is a ligand of the NK cell activating receptor NKG2D. This receptor is essential for NK cell control of tumor development and it has the unique property of being able to recognize tumor cells of both murine and human origin. Here, using atorvastatin and the WM-266-4 melanoma cell line, we first confirmed that statin treatment enhances MICA membrane expression and decreases local tumor growth and pulmonary metastasis implantation in vivo. Furthermore our new experiments showed that atorvastatin intraperitoneal repeated injections induced a reduction of tumor growth following subcutaneous implantation of untreated WM 266-4 cells into NMRI nude mice and favored the innate anti-melanoma immune response by increasing splenic NK cell concentration and activation. This report confirms that statins could become effective pharmacological agents for melanoma immunotherapy.

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