RRC ID 71770
著者 Wakabayashi K, Sakurai F, Ono R, Fujiwara T, Mizuguchi H.
タイトル Development of a Novel Oncolytic Adenovirus Expressing a Short-hairpin RNA Against Cullin 4A.
ジャーナル Anticancer Res
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 AND METHODS: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.
巻・号 40(1)
ページ 161-168
公開日 2020-1-1
DOI 10.21873/anticanres.13937
PII 40/1/161
PMID 31892564
MeSH Adenoviridae / genetics* Animals Cell Line, Tumor Cell Survival / genetics Cullin Proteins / genetics* Gene Expression Gene Knockdown Techniques Genetic Vectors / genetics* Humans Mice Oncolytic Virotherapy Oncolytic Viruses / genetics* RNA Interference RNA, Small Interfering / genetics* Transduction, Genetic
IF 1.994
リソース情報
ヒト・動物細胞 HeLa(RCB0007) HuH-7(RCB1366) Hep G2(RCB1648)