Oncotarget

Research Papers:

Deficiency of caspase 3 in tumor xenograft impairs therapeutic effect of measles virus Edmoston strain

Biao Wang _, Xu Yan, Qingguo Guo, Yan Li, Haiyan Zhang, JiSheng Xie and Xin Meng

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Oncotarget. 2015; 6:16019-16030. https://doi.org/10.18632/oncotarget.3496

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Abstract

Biao Wang1, Xu Yan2, Qingguo Guo1, Yan Li3, Haiyan Zhang4, JiSheng Xie5, Xin Meng1

1Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences of China Medical University Shenyang, P.R. China

2Department of Prosthodontics, School of Stomatology, China Medical University, Shenyang, P.R. China

3Department of Oncology, Tumour Angiogenesis and Microenvironment Laboratory (TAML), First Affiliated Hospital, Liaoning Medical College, Jinzhou, P.R. China

4Department of Geriatrics, The First Affiliated Hospital, China Medical University, Shenyang, P.R. China

5Department 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.


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