ONYX-015 enhances radiation-induced death of human anaplastic thyroid carcinoma cells.
ONYX-015 is a genetically modified adenovirus with a deletion of the E1B early gene and therefore is designed to replicate preferentially in p53-mutated cells causing their death. We previously demonstrated that the ONYX-015 virus kills anaplastic thyroid carcinoma (ATC) cells and enhances the antineoplastic effects of doxorubicin and paclitaxel. Here we report that ONYX-015 increased the cytopathic effect of radiotherapy in three ATC cell lines. In fact, ONYX-015 and radiation induced a significant cytopathic effect on ATC cells. DNA fragmentation analysis showed that ATC ONYX-015-treated cells were very sensitive to radiation-induced apoptosis. In addition, low doses of ONYX-015 associated with a single radiation dose of 10 Gy delayed the growth of a xenograft tumor induced by ARO cells in athymic mice. Our results suggest that the combination of ONYX-015 and radiotherapy should be considered for experimental trials in patients with anaplastic thyroid carcinoma.
Portella
Giuseppe
G
Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università di Napoli Federico II, Naples, Italy. portella@unina.it
Pacelli
Roberto
R
Libertini
Silvana
S
Cella
Laura
L
Vecchio
Giancarlo
G
Salvatore
Marco
M
Fusco
Alfredo
A
D000256:Adenoviridae / Q000235:genetics / Q000276:immunology; D000818:Animals; D002277:Carcinoma / Q000532:radiotherapy*; D016923:Cell Death / Q000528:radiation effects; D003131:Combined Modality Therapy; D053938:DNA Fragmentation / Q000528:radiation effects; D051379:Mice; D008819:Mice, Nude; D011836:Radiation Tolerance; D013964:Thyroid Neoplasms / Q000532:radiotherapy*; D014407:Tumor Cells, Cultured / Q000528:radiation effects; D014765:Viral Vaccines / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
D014765:Viral Vaccines; C464532:dl1520