title: Deficiency of caspase 3 in tumor xenograft impairs therapeutic effect of measles virus Edmoston strain.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences of China Medical University Shenyang, P.R. China.
authors.forename: Biao
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Prosthodontics, School of Stomatology, China Medical University, Shenyang, P.R. China.
authors.forename: Xu
authors.initials: X
authors.lastname: Yan
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences of China Medical University Shenyang, P.R. China.
authors.forename: Qingguo
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Department of Oncology, Tumour Angiogenesis and Microenvironment Laboratory (TAML), First Affiliated Hospital, Liaoning Medical College, Jinzhou, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Geriatrics, The First Affiliated Hospital, China Medical University, Shenyang, P.R. China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Ecsomatics, Youjiang Medical College for Nationalities, Baise City, P.R. China.
authors.forename: Ji Sheng
authors.initials: JS
authors.lastname: Xie
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences of China Medical University Shenyang, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Meng
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D053148:Caspase 3 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008459:Measles virus / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D050130:Oncolytic Virotherapy; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000517:prevention & control* / Q000821:virology; D014779:Virus Replication; D023041:Xenograft Model Antitumor Assays
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; D007371:Interferon-gamma; D053148:Caspase 3
keywords: apoptosis; caspase-3; interferon alpha; measles virus Edmonston strain; oncolytic therapy