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This version published online on August 9, 2007
Endocrinology, doi:10.1210/en.2007-0752
A more recent version of this article appeared on November 1, 2007
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Submitted on June 8, 2007
Accepted on August 2, 2007

LOVASTATIN ENHANCES THE REPLICATION OF THE ONCOLYTIC ADENOVIRUS dl1520 AND ITS ANTINEOPLASTIC ACTIVITY AGAINST ANAPLASTIC THYROID CARCINOMA CELLS

Silvana Libertini, Irma Iacuzzo, Angelo Ferraro, Mario Vitale, Maurizio Bifulco, Alfredo Fusco, and Giuseppe Portella*

Dipartimento di Biologia e Patologia Cellulare e Molecolare and Cattedra di Patologia Clinica Università di Napoli "Federico II"; NOGEC (Naples Oncogenomic Center)-CEINGE, Biotecnologie Avanzate, via Comunale Margherita 482, 80145 Naples, Italy; Dipartimento di Endocrinologia e Oncologia Molecolare e Clinica, Università di Napoli "Federico II", Naples, Italy; Dipartimento di Scienze Farmaceutiche, Università degli Studi di Salerno

* To whom correspondence should be addressed. E-mail: portella{at}unina.it.

Anaplastic thyroid carcinoma (ATC) is one of the most aggressive solid tumors and shows morphological features of a highly malignant, undifferentiated neoplasm. Patients with ATC have a poor prognosis with a mean survival time of 2–6 months; surgery, radiotherapy, and chemotherapy do not improve survival. Gene therapy approaches and oncolytic viruses have been tested for the treatment of ATC.

To enhance the antineoplastic effects of the oncolytic adenovirus dl1520 (Onyx-015), we have treated ATC cells with Lovastatin (3-hydroxy-methylglutaryl-CoA reductase inhibitor), a drug used for the treatment of hypercholesterolemia, which has previously been reported to exert growth inhibitory and apoptotic activity on ATC cells.

Lovastatin treatment significantly increased the effects of dl1520 against ATC cells. The replication of dl1520 in ATC cells was enhanced by lovastatin treatment and a significant increase of the expression of the early gene E1A 13 S and of the late gene Penton was observed in lovastatin treated cells.

Furthermore, lovastatin treatment significantly enhanced the effects of dl1520 against ATC tumour xenografts.

Lovastatin treatment could be exploited to increase the efficacy of oncolytic adenoviruses and further studies are warranted to confirm the feasibility of the approach in ATC patients.


Key words: anaplastic thyroid carcinoma • oncolytic adenovirus • lovastatin







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