The Regulatory Roles Of Spred2 In Human Hepatocellular Carcinoma Cells And Correlative Studies On Its Mechanism

Spred proteins are a recently identified Sprouty-associated membrane protein family.Several reports have indicated that the expression levels of Spred-1 and -2 in human HCC tissue were frequently decreased, comparing with those in adjacent non-tumorous tissue. Moreover, the reduction of Spred expression in HCC is one of the causes of the acquisition of malignant features. On the other hand, Silibinin up-regulates the mRNA levels of Spred-1, Spred-2 in HCC. These results demonstrated that a deficiency of Spred may causes tumorigenesis. Therefore, We establish cells model of HCC (SMMC-7721) to observe the influence of Spred2 on the biological function of SMMC-7721 cells and explore the potential action mechanisms of Spred2 in HCC. In summary, the further research of Spred could provide a potential strategy and targets for the treat-ment of HCC.Firstly, We infected SMMC-7721 cells with an recombinant adenovirus expressing Spred2 (Ad -Spred2) to establish cells model of overexpression Spred2 , further observe the effect of Spred2 on human hepatocellular carcinoma cell line SMMC-7721 cellular proliferation, migration and apoptosis and explore the potential molecular mechanisms of Spred2 in HCC. Our results indicateded that Spred2 could suppress both SMMC-7721 cellular proliferation and migration, Furthermore, Overexpression of Spred2 induces SMMC-7721 cell apoptosis.Secondly, We investigated the potential molecular mechanisms of Spred2 regulating of HCC cell biological functions.The results showed that overexpression of Spred2 could strongly down-regulate the expression of Mcl-1and ERK,Meanwhile, overexpression of Spred2 induced the apoptosis of SMMC-7721 cells through the caspase pathway.To further confirm the roles of inhibition of tumor growth of Spred2. Nude mice were allocated as a model animal to observe effects of Spred2 on tumorigenic activity . The results show that the knockdown of Spred2 enhanced tumor growth in vivo, In contrast , over-expression of Spred2 did not inhibit tumor growth in vivo,Which is different from cells experiment. Therefore, we speculate that Spred2 can regulate tumor growth.Taken together, Spred2 plays a role in the regulation of the biological functions of HCC cells , such as inhibiting proliferation and migration and inducing apoptosis .Preliminary studies have shown that the ERK, Caspase3 and Mcl-1 were involved in Spred2 regulation of the biological characteristics of SMMC-7721 cells.The present works sets up foundations for the further elucidation of the mechanism by which Spred2 regulates HCC cells and provides a potential strategy and targets for the treatment of HCC.