Cisplatin Relocalizes RNA Binding Protein HuR and Enhances the Oncolytic Activity of E4orf6 Deleted Adenovirus
| Autor: | Masumi Tsuda, Aya Yanagawa-Matsuda, Umma Habiba, Asad-uz Zaman, Abu Faem Mohammad Almas Chowdhury, Fumihiro Higashino, Elora Hossain, Shinya Tanaka |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Oncolytic adenovirus
Cancer Research human antigen R RNA-binding protein 3′-untranslated region 3′-UTR lcsh:RC254-282 Article 3 '-UTR Cis-diamminedichloroplatinum (CDDP) Downregulation and upregulation medicine Cisplatin AU-rich element 3 '-untranslated region Chemistry adenovirus MRNA stabilization lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Oncolytic virus ARE Oncology Cancer cell Cancer research HuR medicine.drug |
| Zdroj: | Cancers, Vol 12, Iss 809, p 809 (2020) Cancers Volume 12 Issue 4 |
| ISSN: | 2072-6694 |
| Popis: | The combination of adenoviruses and chemotherapy agents is a novel approach for human cancer therapeutics. A meticulous analysis between adenovirus and chemotherapeutic agents can help to design an effective anticancer therapy. Human antigen R (HuR) is an RNA binding protein that binds to the AU-rich element (ARE) of specific mRNA and is involved in the export and stabilization of ARE-mRNA. Our recent report unveiled that the E4orf6 gene deleted oncolytic adenovirus (dl355) replicated for certain types of cancers where ARE-mRNA is stabilized. This study aimed to investigate whether a combined treatment of dl355 and Cis-diamminedichloroplatinum (CDDP) can have a synergistic cell-killing effect on cancer cells. We confirmed the effect of CDDP in nucleocytoplasmic HuR shuttling. In vitro and in vivo experiments showed the enhancement of cancer cell death by apoptosis induction and a significant reduction in tumor growth following combination treatment. These results suggested that combination therapy exerted a synergistic antitumor activity by upregulation of CDDP induced cytoplasmic HuR, which led to ARE mRNA stabilization and increased virus proliferation. Besides, the enhanced cell-killing effect was due to the activation of the intrinsic apoptotic pathway. Therefore, the combined treatment of CDDP and dl355 could represent a rational approach for cancer therapy. |
| Databáze: | OpenAIRE |
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