1. β-adrenergic receptor inhibition enhances oncolytic herpes virus propagation through STAT3 activation in gastric cancer
- Author
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Yijing He, Ling Chen, Wei Zhang, Jiali Hu, Zhao-Qian Liu, Yu Zhang, Ran Xu, Howard L. McLeod, Cuiyu Chen, Ruitao Lu, Jia Luo, Wei Li, and Qian Hu
- Subjects
Oncolytic virus ,QH301-705.5 ,Propranolol ,QD415-436 ,Biochemistry ,General Biochemistry, Genetics and Molecular Biology ,Oncolytic herpes virus ,Interferon ,medicine ,Viability assay ,Biology (General) ,Innate immunity ,business.industry ,Research ,Cancer ,medicine.disease ,Viral replication ,Type I IFN signaling ,Cancer cell ,Cancer research ,business ,Gastric cancer ,TP248.13-248.65 ,medicine.drug ,Biotechnology - Abstract
Background Oncolytic viruses (OVs) are considered a promising therapeutic alternative for cancer. However, OVs could activate the host innate immunity, then impair the viral propagation in tumor cells. In this study, we explored the effect of propranolol, a non-selective β-blocker, on the antitumor efficacy of T1012G virus in gastric cancer models. Methods The proliferation of gastric cancer cells treated with monotherapy or combination treatment was detected by CCK8 cell proliferation assay. The effect of propranolol was further evaluated by in vitro viral replication assays. In vivo tumor xenograft experiments were used to observe the effect of combination therapy on gastric cancer growth in mice. The expression levels of viral proteins and interferon responsive genes were detected in the gastric cancer cell lines treated with combined treatment by western blot. The impact of propranolol on IFN-α/β-mediated inhibition of viral propagation and the expression of antiviral gene PKR was detected by viral replication assays and western blot. Results Cell viability assay detected a 97.9% decrease of T1012G IC50 in HGC-27 when it was pretreated with propranolol along with a sevenfold increase of virus titers compared with T1012G only group (P 3 vs. 1118 ± 210.0 mm3, P P P P P P P P Conclusions In summary, β-blocker pretreatment could improve the propagation and therapeutic efficacy of T1012G in human gastric cancer by regulating STAT3-PKR signaling cascade, even in the presence of type I IFNs. These data support new strategies of improving the efficacy of OVs in gastric cancer.
- Published
- 2021