Development of a Novel Oncolytic Adenovirus Expressing a Short-hairpin RNA Against Cullin 4A.
Anticancer Res
; 40(1): 161-168, 2020 Jan.
Article
em En
| MEDLINE
| ID: mdl-31892564
ABSTRACT
BACKGROUND:
Arming of an oncolytic adenovirus (OAd) by inserting expression cassettes of therapeutic transgenes into the OAd genome is a promising approach to enhance the therapeutic effects of an OAd. Ideally, this approach would simultaneously promote the replication of an OAd in tumor cells and transgene product-mediated antitumor effects by expressing therapeutic transgenes. We previously demonstrated that knockdown of cullin 4A (CUL4A), which is an E3 ubiquitin ligase, significantly promoted adenovirus replication by increasing the c-JUN protein level. In addition, previous studies reported that CUL4A was highly expressed in various types of tumor, and was involved in tumor growth and metastasis. MATERIALS ANDMETHODS:
In this study, we developed a novel OAd expressing a short-hairpin RNA (shRNA) against CUL4A (OAd-shCUL4A).RESULTS:
OAd-shCUL4 mediated higher levels of cytotoxic effects on various types of human tumor cell than a conventional OAd. Higher levels of OAd genome copy numbers were found in the tumor cells for OAd-shCUL4A, compared with a conventional OAd.CONCLUSION:
OAd-shCUL4A showed efficient antitumor effects by both enhancing OAd replication and inhibiting tumor cell growth.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Adenoviridae
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RNA Interferente Pequeno
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Proteínas Culina
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Vírus Oncolíticos
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Vetores Genéticos
Limite:
Animals
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Humans
Idioma:
En
Revista:
Anticancer Res
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Japão