Inactivated Sendai Virus Induces Apoptosis Mediated by Reactive Oxygen Species in Murine Melanoma Cells

Objective This paper aims to investigate the apoptotic effect of inactivated Sendai virus(hemagglutinating virus of Japan-enveloped,HVJ-E) on murine melanoma cells(B16F10) and the possible mechanisms involved in the putative apoptotic reactions.Methods B16F10 cells were treated with HVJ-E at various multiplicities of infection(MOI),and the reactive oxygen species(ROS),cell viability,and apoptosis were measured.Next,the roles of ROS in the regulation of Bcl-2/Bax and the activation of mitogen-activated protein kinase(MAPK) pathways in HVJ-E-treated B16F10 cells were analyzed.To further evaluate the cytotoxic effect of HVJ-E-generated ROS on B16F10 cells,HVJ-E was intratumorally injected,both with and without N-acetyl-L-cysteine(NAC),into melanoma tumors on BALB/c mice.Tumor volume was then monitored for 3 weeks,and the tumor proteins were separated for immunoblot assay.Results Treatment of B16F10 cells with HVJ-E resulted in a dose-dependent inhibition of cell-viability and an induction of apoptosis.The latter effect was associated with the generation of ROS.Inhibition of ROS generation by NAC resulted in a significant reduction of HVJ-E-induced Erk1/2,JNK,and p38 MAPK activation.Additionally,ROS inhibition caused a decrease in the Bcl-2/Bax ratio as well as promoting activation of apoptosis both in vitro and in vivo.Conclusion These results suggest that HVJ-E possesses potential anticancer activity in B16F10 cells through ROS-mediated mitochondrial dysfunction involving the MAPK pathway.

Sendai virus-based immunoadjuvant in hydrogel vaccine intensity-modulated dendritic cells activation for suppressing tumorigenesis

The conventional immunoadjuvants in vaccine have weak effect on stimulating antigen presentation and activating anti-tumor immunity.Unexpectedly,we discovered that non-pathogenic Sendai virus(SeV)could activate antigen-presenting cells(APCs)represented by dendritic cells(DCs).Here,we designed an injectable SeV-based hydrogel vaccine(SHV)to execute multi-channel recruitment and stimulation of DCs for boosting the specific immune response against tumors.After the release of the NIR-triggered antigens from tumor cells,dendritic cells around the vaccine efficiently transport the antigens to lymph nodes and present them to T lymphocytes,thereby inducing systemic anti-tumor immune memory.Our findings demonstrated that the SHV with excellent universality,convenience and flexibility has achieved better immune protection effects in inhibiting the occurrence of melanoma and breast cancer.In conclusion,the SHV system might serve as the next generation of personalized anti-tumor vaccines with enhanced features over standard vaccination regimens,and represented an alternative way to suppress tumorigenesis.