The Ohio State University College of Medicine, Biomedical Sciences Graduate Program, Columbus, OH 43210, USA.
Nationwide Children's Hospital, Division of Hematology/Oncology/BMT and Center for Childhood Cancer and Blood Diseases, Columbus, OH 43205, USA.
Viruses. 2018 Mar 15;10(3):132. doi: 10.3390/v10030132.
High Mobility Group Box 1 (HMGB1) is a multifunctional protein that plays various roles in the processes of inflammation, cancer, and other diseases. Many reports document abundant HMGB1 release following infection with oncolytic viruses (OVs). Further, other groups including previous reports from our laboratory highlight the synergistic effects of OVs with chemotherapy drugs. Here, we show that virus-free supernatants have varying cytotoxic potential, and HMGB1 is actively secreted by two established fibroblast cell lines (NIH 3T3 and 3T6-Swiss albino) following HSV1716 infection in vitro. Further, pharmacologic inhibition or genetic knock-down of HMGB1 reveals a role for HMGB1 in viral restriction, the ability to modulate bystander cell proliferation, and drug sensitivity in 3T6 cells. These data further support the multifactorial role of HMGB1, and suggest it could be a target for modulating the efficacy of oncolytic virus therapies alone or in combination with other frontline cancer treatments.
高迁移率族蛋白 B1（HMGB1）是一种多功能蛋白，在炎症、癌症和其他疾病的过程中发挥多种作用。许多报道记录了在感染溶瘤病毒（OVs）后大量的 HMGB1 释放。此外，包括我们实验室之前的报告在内的其他研究小组强调了 OVs 与化疗药物的协同作用。在这里，我们表明无病毒上清液具有不同的细胞毒性潜力，并且在体外 HSV1716 感染后，两种已建立的成纤维细胞系（NIH 3T3 和 3T6-Swiss albino）中 HMGB1 被主动分泌。此外，HMGB1 的药理抑制或基因敲低揭示了 HMGB1 在病毒限制、调节旁观者细胞增殖能力以及在 3T6 细胞中药物敏感性方面的作用。这些数据进一步支持了 HMGB1 的多因素作用，并表明它可能是单独或与其他一线癌症治疗联合调节溶瘤病毒治疗效果的靶点。
