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A classical PKA inhibitor increases the oncolytic effect of M1 virus via activation of exchange protein directly activated by cAMP 1

Oncolytic virotherapy is an emerging and promising treatment modality that uses replicating viruses as selective antitumor agents. Here, we report that a classical protein kinase A (PKA) inhibitor, H89, synergizes with oncolytic virus M1 in various cancer cells through activation of Epac1 (exchange...

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Autores principales: Li, Kai, Liang, Jiankai, Lin, Yuan, Zhang, Haipeng, Xiao, Xiao, Tan, Yaqian, Cai, Jing, Zhu, Wenbo, Xing, Fan, Hu, Jun, Yan, Guangmei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5217030/
https://www.ncbi.nlm.nih.gov/pubmed/27374176
http://dx.doi.org/10.18632/oncotarget.10305
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author Li, Kai
Liang, Jiankai
Lin, Yuan
Zhang, Haipeng
Xiao, Xiao
Tan, Yaqian
Cai, Jing
Zhu, Wenbo
Xing, Fan
Hu, Jun
Yan, Guangmei
author_facet Li, Kai
Liang, Jiankai
Lin, Yuan
Zhang, Haipeng
Xiao, Xiao
Tan, Yaqian
Cai, Jing
Zhu, Wenbo
Xing, Fan
Hu, Jun
Yan, Guangmei
author_sort Li, Kai
collection PubMed
description Oncolytic virotherapy is an emerging and promising treatment modality that uses replicating viruses as selective antitumor agents. Here, we report that a classical protein kinase A (PKA) inhibitor, H89, synergizes with oncolytic virus M1 in various cancer cells through activation of Epac1 (exchange protein directly activated by cAMP 1). H89 substantially increases viral replication in refractory cancer cells, leading to unresolvable Endoplasmic Reticulum stress, and cell apoptosis. Microarray analysis indicates that H89 blunts antiviral response in refractory cancer cells through retarding the nuclear translocation of NF-κB. Importantly, in vivo studies show significant antitumor effects during M1/H89 combination treatment. Overall, this study reveals a previously unappreciated role for H89 and demonstrates that activation of the Epac1 activity can improve the responsiveness of biotherapeutic agents for cancer.
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spelling pubmed-52170302017-01-17 A classical PKA inhibitor increases the oncolytic effect of M1 virus via activation of exchange protein directly activated by cAMP 1 Li, Kai Liang, Jiankai Lin, Yuan Zhang, Haipeng Xiao, Xiao Tan, Yaqian Cai, Jing Zhu, Wenbo Xing, Fan Hu, Jun Yan, Guangmei Oncotarget Research Paper Oncolytic virotherapy is an emerging and promising treatment modality that uses replicating viruses as selective antitumor agents. Here, we report that a classical protein kinase A (PKA) inhibitor, H89, synergizes with oncolytic virus M1 in various cancer cells through activation of Epac1 (exchange protein directly activated by cAMP 1). H89 substantially increases viral replication in refractory cancer cells, leading to unresolvable Endoplasmic Reticulum stress, and cell apoptosis. Microarray analysis indicates that H89 blunts antiviral response in refractory cancer cells through retarding the nuclear translocation of NF-κB. Importantly, in vivo studies show significant antitumor effects during M1/H89 combination treatment. Overall, this study reveals a previously unappreciated role for H89 and demonstrates that activation of the Epac1 activity can improve the responsiveness of biotherapeutic agents for cancer. Impact Journals LLC 2016-06-27 /pmc/articles/PMC5217030/ /pubmed/27374176 http://dx.doi.org/10.18632/oncotarget.10305 Text en Copyright: © 2016 Li et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Li, Kai
Liang, Jiankai
Lin, Yuan
Zhang, Haipeng
Xiao, Xiao
Tan, Yaqian
Cai, Jing
Zhu, Wenbo
Xing, Fan
Hu, Jun
Yan, Guangmei
A classical PKA inhibitor increases the oncolytic effect of M1 virus via activation of exchange protein directly activated by cAMP 1
title A classical PKA inhibitor increases the oncolytic effect of M1 virus via activation of exchange protein directly activated by cAMP 1
title_full A classical PKA inhibitor increases the oncolytic effect of M1 virus via activation of exchange protein directly activated by cAMP 1
title_fullStr A classical PKA inhibitor increases the oncolytic effect of M1 virus via activation of exchange protein directly activated by cAMP 1
title_full_unstemmed A classical PKA inhibitor increases the oncolytic effect of M1 virus via activation of exchange protein directly activated by cAMP 1
title_short A classical PKA inhibitor increases the oncolytic effect of M1 virus via activation of exchange protein directly activated by cAMP 1
title_sort classical pka inhibitor increases the oncolytic effect of m1 virus via activation of exchange protein directly activated by camp 1
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5217030/
https://www.ncbi.nlm.nih.gov/pubmed/27374176
http://dx.doi.org/10.18632/oncotarget.10305
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