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Open Access Research article

Adaptation to statins restricts human tumour growth in Nude mice

Julie Follet1, Lionel Rémy2, Vincent Hesry3, Brigitte Simon1, Danièle Gillet1, Pierrick Auvray3, Laurent Corcos1 and Catherine Le Jossic-Corcos1*

Author Affiliations

1 INSERM U613-ECLA and IFR148-ScInBioS, Université Européenne de Bretagne, Université de Bretagne Occidentale, Faculté de médecine, 22 avenue Camille Desmoulins, 29200 Brest, France

2 INSERM U865, Faculté de Médecine RTH Laennec, 7 rue Guillaume Paradin, 69372 Lyon cedex 08, France

3 C.Ris Pharma, Parc Technopolitain - Atalante Saint-Malo, 35400 Saint Malo, France

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BMC Cancer 2011, 11:491  doi:10.1186/1471-2407-11-491

Published: 22 November 2011

Abstract

Background

Statins have long been used as anti-hypercholesterolemia drugs, but numerous lines of evidence suggest that they may also bear anti-tumour potential. We have recently demonstrated that it was possible to isolate cancer cells adapted to growth in the continuous presence of lovastatin. These cells grew more slowly than the statin-sensitive cells of origin. In the present study, we compared the ability of both statin-sensitive and statin-resistant cells to give rise to tumours in Nude mice.

Methods

HGT-1 human gastric cancer cells and L50 statin-resistant derivatives were injected subcutaneously into Nude mice and tumour growth was recorded. At the end of the experiment, tumours were recovered and marker proteins were analyzed by western blotting, RT-PCR and immunohistochemistry.

Results

L50 tumours grew more slowly, showed a strong decrease in cyclin B1, over-expressed collagen IV, and had reduced laminin 332, VEGF and CD34 levels, which, collectively, may have restricted cell division, cell adhesion and neoangiogenesis.

Conclusions

Taken together, these results showed that statin-resistant cells developed into smaller tumours than statin-sensitive cells. This may be reflective of the cancer restricting activity of statins in humans, as suggested from several retrospective studies with subjects undergoing statin therapy for several years.

Keywords:
Statins, Gastric cancer; Nude mice; Apoptosis, Angiogenesis