A recombinant measles virus vaccine strain rMV-Hu191 has oncolytic effect against human gastric cancer by inducing apoptotic cell death requiring integrity of lipid raft microdomains.

Autor: Lv Y; Zhejiang University School of Medicine, Hangzhou, 310000, Zhejiang, China. Electronic address: 21418068@zju.edu.cn., Zhou D; Zhejiang University School of Medicine, Hangzhou, 310000, Zhejiang, China. Electronic address: 11318120@zju.edu.cn., Hao XQ; Zhejiang University School of Medicine, Hangzhou, 310000, Zhejiang, China. Electronic address: 11718196@zju.edu.cn., Zhu MY; Zhejiang University School of Medicine, Hangzhou, 310000, Zhejiang, China. Electronic address: 11618182@zju.edu.cn., Zhang CD; Zhejiang University School of Medicine, Hangzhou, 310000, Zhejiang, China. Electronic address: 21718442@zju.edu.cn., Zhou DM; Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310052, Zhejiang, China. Electronic address: 21318243@zju.edu.cn., Wang JH; Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310052, Zhejiang, China. Electronic address: wjh@zju.edu.cn., Liu RX; Zhejiang University School of Medicine, Hangzhou, 310000, Zhejiang, China. Electronic address: 21618412@zju.edu.cn., Wang YL; Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310052, Zhejiang, China. Electronic address: 11418155@zju.edu.cn., Gu WZ; Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310052, Zhejiang, China; Key Laboratory of Diagnosis and Treatment of Neonatal Diseases of Zhejiang Province, Hangzhou, 310052, Zhejiang, China. Electronic address: 6195013@zju.edu.cn., Shen HQ; Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310052, Zhejiang, China; Key Laboratory of Diagnosis and Treatment of Neonatal Diseases of Zhejiang Province, Hangzhou, 310052, Zhejiang, China. Electronic address: shenhq@zju.edu.cn., Chen X; Zhejiang University School of Medicine, Hangzhou, 310000, Zhejiang, China; Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310052, Zhejiang, China; Key Laboratory of Diagnosis and Treatment of Neonatal Diseases of Zhejiang Province, Hangzhou, 310052, Zhejiang, China. Electronic address: chchenxi@zju.edu.cn., Zhao ZY; Zhejiang University School of Medicine, Hangzhou, 310000, Zhejiang, China; Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310052, Zhejiang, China; Key Laboratory of Diagnosis and Treatment of Neonatal Diseases of Zhejiang Province, Hangzhou, 310052, Zhejiang, China. Electronic address: zhaozy@zju.edu.cn.
Jazyk: angličtina
Zdroj: Cancer letters [Cancer Lett] 2019 Sep 28; Vol. 460, pp. 108-118. Date of Electronic Publication: 2019 Jun 19.
DOI: 10.1016/j.canlet.2019.06.010
Abstrakt: Live-attenuated strain of measles virus (MV) has oncolytic effect. In this study, the antitumor effect of rMV-Hu191, a recombinant Chinese Hu191 MV generated in our laboratory by efficient reverse genetics system, was evaluated in gastric cancer (GC). From our data, rMV-Hu191 induced cytopathic effects and inhibited tumor proliferation both in vitro and in vivo by inducing caspase-dependent apoptosis. In mice bearing GC xenografts, tumor size was reduced and survival was prolonged significantly after intratumoral injections of rMV-Hu191. Furthermore, lipid rafts, a type of membrane microdomain with specific lipid compositions, played an important role in facilitating entry of rMV-Hu191. Integrity of lipid rafts was required for successful viral infection as well as subsequent cell apoptosis, but was not required for viral binding and replication. CD46, a MV membrane receptor, was found to be partially localized in lipid rafts microdomains. This is the first study to demonstrate that Chinese Hu191 MV vaccine strain could be used as a potentially effective therapeutic agent in GC treatment. As part of the underlying cellular mechanism, the integrity of lipid rafts is required for viral entry and to exercise the oncolytic effect.
(Copyright © 2019 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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