仙台病毒(HVJ)诱生IFNβ可致肿瘤细胞凋亡，并干扰小鼠移植瘤模型建立。研究证实，除JAK/STAT外，HVJ诱生IFNβ一定存在其他未知信号通路可致肿瘤细胞凋亡。本项目前期研究表明：HVJ诱生IFNβ可致小鼠黑色素瘤细胞凋亡，并首次证实其中的胰岛素样生长因子1受体(IGF-1R)表达下降，但具体的调控机制尚未阐明。为进一步研究HVJ致肿瘤细胞凋亡的分子机制，本项目以IFNβ为切入点，用IFNα/β受体抗体或siRNA阻断I型干扰素信号通路，并用JAK抑制剂封闭JAK/STAT通路，阐明HVJ诱生IFNβ对IGF-1R表达的调控；并通过流式细胞术、免疫印迹和免疫组化等手段，从体内、外两个层面，研究HVJ诱生IFNβ对IGF-1R下游调控的PI3K-Akt和MAPK信号通路的影响，旨在明确HVJ诱生IFNβ致肿瘤细胞凋亡的新途径，为进一步阐明HVJ干扰小鼠移植瘤模型建立的机制提供科学依据。

Hemagglutinating virus of Japan (HVJ) can induce interforn-β (IFN-β), causing apoptosis in tumor cells and interfering with the establishment of transplanted tumor models in mice. In addition to the Janus kinases/signal transducers and activators of transcription (JAK/STAT) signaling pathway, there are other evidences demonstrating that IFN-β induced by HVJ could induce apoptosis in cancer cells by still unknown signaling pathways. Our previous study indicated that HVJ-induced IFN-β could induce apoptosis in murine melanoma cells, and the down-expression of insulin-like growth factor-1 receptor (IGF-1R) by HVJ in the cells was first discovered. However, the specific mechanism to this remains unknown. To further investigate the mechanism of apoptotic induction by HVJ in tumor cells，in this project, interferon α/β receptor antibody or siRNA specific to interferon-β promoter stimulator 1 (IPS-1) is going to be used to block the type I interferon signaling pathway, and JAK inhibitor will be used to block the JAK/STAT signaling pathway. Through the detection of IFN-β and IGF-1R expression, the relationship between HVJ-induced IFN-β and the IGF-1R expression is aiming to be elucidated. In addition, fluorescence-activated cell sorter (FACS), immunohistochemistry and immunoblot analysis will be carried out to investigate the effect of HVJ-induced IFN-β on phosphatidylinositol 3-kinase/Serine/threonine Kinase (PI3K/Akt) and mitogen-activated protein kinase (MAPK) signaling pathways in vitro and in vivo. Based on the above studies, this research has the potential to throw light on new mechanisms in apoptosis induction by HVJ-induced IFN-β in tumor cells, and provide scientific evidences to further elucidate the mechanisms in interfering with the establishment of tumor models by HVJ.