Research Papers:

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

Kai Li, Jiankai Liang, Yuan Lin, Haipeng Zhang, Xiao Xiao, Yaqian Tan, Jing Cai, Wenbo Zhu, Fan Xing, Jun Hu and Guangmei Yan _

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Oncotarget. 2016; 7:48443-48455. https://doi.org/10.18632/oncotarget.10305

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Kai Li1,*, Jiankai Liang1,*, Yuan Lin1,*, Haipeng Zhang1, Xiao Xiao1,4, Yaqian Tan1, Jing Cai1, Wenbo Zhu1, Fan Xing1, Jun Hu2, Guangmei Yan1,3

1Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China

2Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China

3Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou 510080, China

4Department of Pharmacy, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China

*These authors have contributed equally to this work

Correspondence to:

Guangmei Yan, email: [email protected]

Jun Hu, email: [email protected]

Keywords: oncolytic virus, M1 virus, Epac1, H89, innate immunity

Received: May 11, 2016     Accepted: June 09, 2016     Published: June 27, 2016


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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