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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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