Effect and Mechanism of HMGB1 on Immune Efficacy of Recombinant Adenovirus Vector-based Human Papillomavirus-16 Vaccine

OBJECTIVE To study the influence of HMGB1 on the effect of recombinant adenovirus vector-based human papillomavirus-16 vaccine in mice model and explore the potential mechanism.METHODS HMGB1 antagonist, HMGB1 A box protein was injected into the model mice resulting from TC-1 cell transplantation. Anti-tumor test, immunological influence observation and tumor associated signaling molecules test were carried out with ecombinant adenovirus vector-based human papillomavirus-16 vaccination. RESULTS A box and vaccine combinating injection could decrease the serum HMGB1 level and inhibit NF-κB mRNA expression in model mice, accompanied with a lower tumor occurrence. It also regulated Th1/Th2 type cytokines balance by inducing IFN-γ and decreasing IL-4. And compared with model control group, HMGB1 inhibiting made the vaccine played a better performance in reducing NF-κB, Bcl-2, c-IAP2, VEGF, MMP-9 expression and increasing Bax expression in tumor model mice. CONCLUSION HMGB1 can block the immune response and anti-tumor effect of recombinant adenovirus vector-based human papillomavirus-16 vaccine in mouse model, and it probably resulted from HMGB1 playing an important role in cell apoptosis, tumor invasion and metastasis and immune balance regulation.