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Lovastatin Enhances the Replication of the Oncolytic Adenovirus dl1520 and Its Antineoplastic Activity against Anaplastic Thyroid Carcinoma Cells

Dipartimenti di Biologia e Patologia Cellulare e Molecolare (S.L., I.I., A.Fu., G.P.) and Endocrinologia e Oncologia Molecolare e Clinica (M.V.), and Cattedra di Patologia Clinica (G.P.), Università di Napoli "Federico II," 80131 Napoli, Italy; Naples Oncogenomic Center-Centro Ingegneria Genetica (A.Fe., A.Fu.), Biotecnologie Avanzate, 80145 Naples, Italy; and Dipartimento di Scienze Farmaceutiche (M.B.), Università degli Studi di Salerno, 84084 Naples, Italy

Address all correspondence and requests for reprints to: Giuseppe Portella, Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università di Napoli Federico II, via S. Pansini 5, 80131 Napoli, Italy. 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 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 the late gene Penton was observed in lovastatin-treated cells. Furthermore, lovastatin treatment significantly enhanced the effects of dl1520 against ATC tumor 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.