High Mobility Group Box 1 Influences HSV1716 Spread and Acts as an Adjuvant to Chemotherapy.
Leslee SpragueJoel M LeeBrian J HutzenPin-Yi WangChun-Yu ChenJoe ConnerLynne BraidwoodKevin A CassadyTimothy P CripePublished in: Viruses (2018)
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.
Keyphrases
- cell proliferation
- papillary thyroid
- transcription factor
- oxidative stress
- early stage
- emergency department
- binding protein
- locally advanced
- adverse drug
- drug delivery
- sars cov
- squamous cell
- signaling pathway
- gene expression
- squamous cell carcinoma
- genome wide
- young adults
- radiation therapy
- drug induced
- human health
- risk assessment
- childhood cancer
- amino acid
- protein protein
- pi k akt