Gene silencing with siRNA targeting E6/E7 as a therapeutic intervention against head and neck cancer-containing HPV16 cell lines.
Acta Otolaryngol
; 133(7): 761-71, 2013 Jul.
Article
en En
| MEDLINE
| ID: mdl-23638950
ABSTRACT
CONCLUSION:
Our results indicate that siRNA E6 and/or E7 may have potential as a gene-specific therapy for human papillomavirus (HPV) type 16 (HPV16)-related squamous cell carcinoma of the head and neck (HNSCC).OBJECTIVES:
To evaluate the effectiveness of siRNA targeting E6 and/or E7 on the in vitro and in vivo growth suppression of HPV16-related HNSCC.METHODS:
HPV16-related HNSCC (UM-SCC47) cell lines were used for the present study. Expression of HPV viral oncogenes E6 and/or E7 and their cellular targets, p53 and pRb, was evaluated by real-time PCR, Western blotting, and immunofluorescence staining. To study the effect of siRNA on tumor growth in vivo, we developed animal models. Representative tumors harvested from each group were processed for apoptosis analyses (TUNEL assay) and immunofluorescence staining for p53 and pRb.RESULTS:
E6 and E7 oncogenes of HPV16 were down-regulated by E6 and/or E7 targeting siRNAs, respectively. The expression of p53 and pRb proteins in both the E6 siRNA group and E7 siRNA group was up-regulated compared with those of control groups. The cellular proliferation and apoptosis indexes of E6 and/or E7 siRNA groups were higher than those of controls. In vivo studies showed significant inhibitory effect of E6 and/or E7 siRNA compared with those of control groups, which was consistent with in vitro studies.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas Represoras
/
Carcinoma de Células Escamosas
/
Proteínas Oncogénicas Virales
/
ARN Interferente Pequeño
/
Proteínas E7 de Papillomavirus
/
Terapia Molecular Dirigida
/
Neoplasias de Cabeza y Cuello
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Acta Otolaryngol
Año:
2013
Tipo del documento:
Article
País de afiliación:
Japón