Eradication of cervical cancer in vivo by an AAV vector that encodes shRNA targeting human papillomavirus type 16 E6/E7.
Int J Oncol
; 52(3): 687-696, 2018 Mar.
Article
en En
| MEDLINE
| ID: mdl-29344635
ABSTRACT
The major causative agent of cervical cancer is human papilloma virus (HPV); the viral proteins E6 and E7 induce carcinogenesis through the inactivation of the host tumor-suppressor gene. Therefore, the stable expression of specific inhibitors of E6 and E7 in cancer cells is expected to provide effective treatment for cervical cancer without affecting normal tissue. In this study, we propose a novel therapeutic approach using an adeno-associated virus (AAV) vector encoding short hairpin RNA (shRNA) against the oncoproteins E6 and E7 (shE6E7) of HPV type 16 (HPV16), termed AAVshE6E7. Three different HPV16-positive cervical cancer cell lines (BOKU, SiHa and SKG-IIIa cells) were tested for gene transfer efficiency using serotypes of AAV vectors. For in vitro analysis, the cells were transduced AAVshE6E7; alternatively, in vivo studies were performed via the administration of a direct injection of AAVshE6E7 into cervical cancer cell-derived tumors in mice. The high gene transfer efficiency was observed using AAV2 in all three cervical cancer cell lines. Following transduction, we observed apoptosis, G1 phase arrest and cell growth inhibition. Additionally, in the transduced cells, the E6, E7 and p16 expression levels decreased, whereas the expression levels of p53, p21 and pRb levels were enhanced. The growth of subcutaneously transplanted tumors was markedly inhibited by the single administration of AAV2shE6E7, and the tumors were almost completely eradicated without any adverse effects. These results provided evidence of the utility of AAV2shE6E7 as a novel treatment approach for cervical cancer.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
2_ODS3
/
6_ODS3_enfermedades_notrasmisibles
Problema de salud:
2_enfermedades_transmissibles
/
6_cervical_cancer
Asunto principal:
Neoplasias del Cuello Uterino
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Dependovirus
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Infecciones por Papillomavirus
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ARN Interferente Pequeño
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Papillomavirus Humano 16
/
Vectores Genéticos
Tipo de estudio:
Evaluation_studies
/
Prognostic_studies
Límite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Int J Oncol
Asunto de la revista:
NEOPLASIAS
Año:
2018
Tipo del documento:
Article
País de afiliación:
Japón