Deficiency of caspase 3 in tumor xenograft impairs therapeutic effect of measles virus Edmoston strain
| Autor: | Ji Sheng Xie, Biao Wang, Haiyan Zhang, Yan Li, Xu Yan, Qing-guo Guo, Xin Meng |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
caspase-3
Blotting Western Alpha interferon Mice Nude Uterine Cervical Neoplasms Caspase 3 Apoptosis Real-Time Polymerase Chain Reaction Virus Replication Virus measles virus Edmonston strain Measles virus Interferon-gamma Mice Tumor Cells Cultured Medicine interferon alpha Animals Humans Interferon gamma RNA Messenger RNA Small Interfering Cell Proliferation Oncolytic Virotherapy Mice Inbred BALB C biology business.industry oncolytic therapy Reverse Transcriptase Polymerase Chain Reaction biology.organism_classification Flow Cytometry Virology Xenograft Model Antitumor Assays Oncolytic virus Oncology Viral replication Female business medicine.drug Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // Biao Wang 1 , Xu Yan 2 , Qingguo Guo 1 , Yan Li 3 , Haiyan Zhang 4 , JiSheng Xie 5 , Xin Meng 1 1 Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences of China Medical University Shenyang, P.R. China 2 Department of Prosthodontics, School of Stomatology, China Medical University, Shenyang, P.R. China 3 Department of Oncology, Tumour Angiogenesis and Microenvironment Laboratory (TAML), First Affiliated Hospital, Liaoning Medical College, Jinzhou, P.R. China 4 Department of Geriatrics, The First Affiliated Hospital, China Medical University, Shenyang, P.R. China 5 Department of Ecsomatics, Youjiang Medical College for Nationalities, Baise City, P.R. China Correspondence to: Xin Meng, e-mail: kinmou0423@hotmail.com Keywords: caspase-3, interferon alpha, oncolytic therapy, apoptosis, measles virus Edmonston strain Received: January 20, 2015 Accepted: March 07, 2015 Published: March 26, 2015 ABSTRACT The oncolytic measles virus Edmonston (MV-Edm) strain shows considerable oncolytic activity against a variety of human tumors. In this study, we report MV-Edm is able to trigger apoptosis pathways in infected tumor cells and elucidate the roles of cellular apoptosis in the whole oncolytic process. We also show that activated caspase 3, a key executioner of apoptosis, plays key roles in the oncolytic virotherapy. Activated caspase 3 can accelerate viral replication in cervical cancer cells and enhance the killing effects of the virus. Deficiency of caspase 3 either in tumor cells or in tumor xenograft significantly desensitized tumor to oncolysis with MV-Edm. In the infected cells, caspase 3 regulates interferon α release, which can inhibit viral replication in neighboring tumor cells. We propose that caspase-3 activation enhances the oncolytic effects of MV-Edm, thus inhibiting tumor growth in mice. |
| Databáze: | OpenAIRE |
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