ONYX-015, an E1B gene-defective adenovirus, induces cell death in human anaplastic thyroid carcinoma cell lines.
Being one of the most lethal human neoplasms and refractory to such conventional treatment as chemo- and radiotherapy, anaplastic thyroid carcinoma is a prime target for innovative therapy. p53 gene inactivation is a constant feature of this neoplasia. Therefore, we evaluated a therapeutic approach based on an E1B 55-kDa gene-defective adenovirus (ONYX-015) that replicates only in cells with impaired p53 function and leads to cell death. Here we report that the ONYX-015 virus induces cell death in three human thyroid anaplastic carcinoma cell lines (ARO, FRO, and KAT-4). In addition, we found that the growth of xenograft tumors induced in athymic mice by the injection of ARO cells was drastically reduced by ONYX-015 treatment. The ONYX-015 virus worked synergistically with two antineoplastic drugs (doxorubicin and paclitaxel) in inducing ARO and KAT-4 cell death. These results suggest that ONYX-015 may be a valid tool in the treatment of the human thyroid anaplastic carcinoma.
Portella
Giuseppe
G
Department of Biology and Cellular and Molecular Pathology, Faculty of Medicine and Surgery, Federico II University of Naples, via S. Pansini 5, 80131 Naples, Italy. portella@unina.it
Scala
Stefania
S
Vitagliano
Donata
D
Vecchio
Giancarlo
G
Fusco
Alfredo
A
D018263:Adenocarcinoma, Follicular / Q000473:pathology / Q000503:physiopathology; D017501:Adenovirus E1B Proteins / Q000235:genetics*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D015197:Carcinogenicity Tests; D002277:Carcinoma / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control / Q000821:virology*; D002291:Carcinoma, Papillary / Q000473:pathology / Q000503:physiopathology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D003673:Defective Viruses / Q000235:genetics / Q000502:physiology*; D004317:Doxorubicin / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D017239:Paclitaxel / Q000494:pharmacology; D051381:Rats; D013964:Thyroid Neoplasms / Q000473:pathology / Q000503:physiopathology* / Q000821:virology*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured / Q000187:drug effects
D017501:Adenovirus E1B Proteins; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D004317:Doxorubicin; D017239:Paclitaxel