Simvastatin reduces melanoma progression in a murine model

Zanfardino,Mario; Spampanato,Carmine; De Cicco,Rosanna; Buommino,Elisabetta; De Filippis,Anna; Baiano,Salvatore; Barra,Adriano; Morelli,Franco

doi:10.3892/ijo.2013.2126

Simvastatin reduces melanoma progression in a murine model

Authors:
- Mario Zanfardino
- Carmine Spampanato
- Rosanna De Cicco
- Elisabetta Buommino
- Anna De Filippis
- Salvatore Baiano
- Adriano Barra
- Franco Morelli
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Affiliations: Institute of Genetics and Biophysics A. Buzzati Traverso, CNR Naples, Naples, Italy, Telethon Institute of Genetics and Medicine, Naples, Italy, Department of Experimental Medicine, Second University of Naples, Naples, Italy
Published online on: October 4, 2013 https://doi.org/10.3892/ijo.2013.2126
Pages: 1763-1770
Copyright: © Zanfardino et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Statins are a class of drugs that inhibit the rate-limiting step in the cholesterol biosynthetic pathway and show an anticancer effect, probably through the inhibition of cell proliferation. To date, the exact mechanism of cancer cell growth arrest induced by statins is not known. We report that simvastatin is able to induce apoptosis in melanoma cells but not in normal cells and also able to contrast the growth of tumor in an experimental melanoma murine model. We observed a delay in the tumor development in almost the 50% of the simvastatin administered animals and a strong reduction of the tumor volume with a differences of ~150% compared to the controls. Also the survival rate was significantly higher in mice that received the drug with a survival increase of ~130% compared to the controls. The tumor growth reduction in mice was supported by the results of cell migration assay, confirming that simvastatin clearly reduced cell migration. Moreover, simvastatin induced a strong downregulation of NonO gene expression, an important growth factor involved in the splicing regulation. This result could explain the decrease of melanoma cells proliferation, suggesting a possible action mechanism. The results derived from our experiments may sustain the many reports on the anticancer inhibitory property of statins and encourage new studies on this drug for a possible use in therapy, probably in combination with conventional chemotherapy.

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