肿瘤细胞浸润和转移的生物学行为始终是关注的交点。anoikis 指细胞失去了粘附而诱导凋亡。瘤细胞具有抗脱落凋亡的作用。研究表明FXa和uPA促进了肿瘤细胞的浸润转移。氧化磷酸化和线粒体呼吸链产物与肿瘤细胞脱落凋亡也密切相关。Serp－1是粘液瘤病毒来源的具有抑制FXa 和uPA功能的蛋白质。本研究拟采用shRNA技术和pDEST17过表达载体建立FXa，uPA低和高表达肝肿瘤细胞系，研究它们在肝肿瘤脱落凋亡中的作用，评价Serp－1的功能。在此基础上使用LDH,PDH,PDK 和ROS的抑制剂研究氧化磷酸化和线粒体呼吸链途径是否是Serp－1促进脱落凋亡的可能机制。通过使用重症免疫缺陷小鼠，和联合FXa或uPA基因敲除小鼠，和联合注射人体外周血单个核细胞建立三种瘤细胞转移的动物模型，在体内探索Serp－1是否通过抑制FXa，uPA和调节机体免疫细胞促进肝肿瘤细胞的脱落凋亡。

The biological behaviors of tumor cells characterized by invasion and metastasis are always concerned for ages. Anoikis medically refers cells lose the ability of adhesion and then undergo apoptosis. Tumor cells are endowed to resistance to anoikis. Studies have shown that the clotting factor (FXa) and fibrinolytic factors (uPA) promoted invasion and metastasis of tumor cells and that the oxidative phosphorylation pathway (LDH, PDH, PDK), and mitochondrial respiratory chain products (ROS) are also closely related to tumor cell anoikis. Serp-1 protein derived from myxoma virus can directly inhibits FXa and uPA. To study the role of FXa and uPA in the liver tumor anoikis and explore if Serp-1 potentially promote anoikis through the mitochondrial metabolism and respiratory chain pathway, using shRNA technology and pDEST17 Gate way over-expression vector in our study to establish the stable liver cancer cell lines with FXa or uPA low and high expression to evaluate the levels of anoikis and the role of Serp-1 on anoikis in vitro. On the basis of previous experiments, LDH, PDH, PDK, and ROS inhibitors will be used to confirm the effect of oxidative phosphorylation and mitochondrial respiratory chain pathways on tumor cell anoikis. Through the use of severe combined immune defects (SCID) mice , SCID mice plus FXa or uPA gene knockout , and SCID mice injected with human peripheral blood mononuclear cells to establish three types of animal models to futher confirm whether Serp-1 can promote anoikis of liver tumor cells in vivo by inhibiting FXa, uPA, and modulation of immune cells.