β-adrenergic receptor inhibition enhances oncolytic herpes virus propagation through STAT3 activation in gastric cancer

Abstract Background Oncolytic viruses (OVs) are considered a promising therapeutic alternative for cancer. However, OVs could activate the host innate immunity, then impair viral propagation in tumor cells. In this study, we explored effect of propranolol, non-selective β-blocker, on antitumor efficacy T1012G virus gastric cancer models. Methods The proliferation cells treated with monotherapy or combination treatment was detected by CCK8 cell assay. propranolol further evaluated vitro replication assays. vivo xenograft experiments were used to observe therapy growth mice. expression levels proteins and interferon responsive genes lines combined western blot. impact IFN-α/β-mediated inhibition antiviral gene PKR assays Results Cell viability assay 97.9% decrease IC50 HGC-27 when it pretreated along sevenfold increase titers compared only group ( P < 0.001). Moreover, pretreatment caused sustained regression (335.3 ± 36.92 mm 3 vs. 1118 210.0 , 0.01) enhanced (fourfold increase, group. Propranolol significantly p-STAT3 (2.9-fold, 0.05) suppressed p-PKR (65.94% 10.11%, addition, counteract (compared IFNα: 5.1-fold, 0.001; IFNβ: 4.6-fold, enhancement activation (IFNα: 92.57% 1.77%, 0.001, 99.34% 0.13% decrease, Conclusions summary, β-blocker improve human regulating STAT3-PKR signaling cascade, even presence type I IFNs. These data support new strategies improving