Lovastatin enhances the replication of the oncolytic adenovirus dl1520 and its antineoplastic activity against anaplastic thyroid carcinoma cells.
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.
Libertini
Silvana
S
Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università di Napoli Federico II, via S Pansini 5, 80131, Napoli, Italy.
Iacuzzo
Irma
I
Ferraro
Angelo
A
Vitale
Mario
M
Bifulco
Maurizio
M
Fusco
Alfredo
A
Portella
Giuseppe
G
D000256:Adenoviridae / Q000187:drug effects*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy / Q000628:therapy*; D002478:Cells, Cultured; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D008148:Lovastatin / Q000494:pharmacology* / Q000627:therapeutic use*; D051379:Mice; D008819:Mice, Nude; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000187:drug effects; D013964:Thyroid Neoplasms / Q000628:therapy*; D014765:Viral Vaccines; D014779:Virus Replication / Q000187:drug effects*; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D014765:Viral Vaccines; C464532:dl1520; D008148:Lovastatin