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.
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| Abstract |
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.
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| Authors | Yao Lv, Duo Zhou, Xiao-Qiang Hao, Meng-Ying Zhu, Chu-di Zhang, Dong-Ming Zhou, Jin-Hu Wang, Rong-Xian Liu, Yi-Long Wang, Wei-Zhong Gu, Hong-Qiang Shen, Xi Chen, Zheng-Yan Zhao |
| Journal | Cancer letters (Cancer Lett) Vol. 460 Pg. 108-118 (Sep 28 2019) ISSN: 1872-7980 [Electronic] Ireland |
| PMID | 31226409 (Publication Type: Journal Article) |
| Copyright | Copyright © 2019 Elsevier B.V. All rights reserved. |
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