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Advantages of Using Paclitaxel in Combination with Oncolytic Adenovirus Utilizing RNA Destabilization Mechanism

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Title: Advantages of Using Paclitaxel in Combination with Oncolytic Adenovirus Utilizing RNA Destabilization Mechanism
Authors: Hossain, Elora Browse this author
Habiba, Umma Browse this author →KAKEN DB
Yanagawa-Matsuda, Aya Browse this author →KAKEN DB
Alam, Arefin Browse this author
Ahmed, Ishraque Browse this author
Alam, Mohammad Towfik Browse this author →KAKEN DB
Yasuda, Motoaki Browse this author →KAKEN DB
Higashino, Fumihiro Browse this author →KAKEN DB
Keywords: Oncolytic adenovirus
E1A
AU-rich element (ARE)
HuR
ARE-mRNA
Paclitaxel
Microtubules
CAR
Issue Date: May-2020
Publisher: MDPI
Journal Title: Cancers
Volume: 12
Issue: 5
Start Page: 1210
Publisher DOI: 10.3390/cancers12051210
Abstract: Oncolytic virotherapy is a novel approach to cancer therapy. Ad-fosARE is a conditionally replicative adenovirus engineered by inserting AU-rich elements (ARE) in the 3'-untranslated region of the E1A gene. In this study, we examined the oncolytic activity of Ad-fosARE and used it in a synergistic combination with the chemotherapeutic agent paclitaxel (PTX) for treating cancer cells. The expression of E1A was high in cancer cells due to stabilized E1A-ARE mRNA. As a result, the efficiency of its replication and cytolytic activity in cancer cells was higher than in normal cells. PTX treatment increased the cytoplasmic HuR relocalization in cancer cells, enhanced viral replication through elevated E1A expression, and upregulated CAR (Coxsackie-adenovirus receptor) required for viral uptake. Furthermore, PTX altered the instability of microtubules by acetylation and detyrosination, which is essential for viral internalization and trafficking to the nucleus. These results indicate that PTX can provide multiple advantages to the efficacy of Ad-fosARE both in vitro and in vivo, and provides a basis for designing novel clinical trials. Thus, this virus has a lot of benefits that are not found in other oncolytic viruses. The virus also has the potential for treating PXT-resistant cancers.
Rights: https://creativecommons.org/licenses/by/4.0/
Type: article
URI: http://hdl.handle.net/2115/78874
Appears in Collections:歯学院・歯学研究院 (Graduate School of Dental Medicine / Faculty of Dental Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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