Abstract: Objective: To explore the inhibitory effect of Tum-5 gene on the tumor growth and its influence in the angiogenesis of hepatocellular carcinoma (HCC),and to illustrate its mechanism involved in anti-tumorigenesis. Methods: The human HepG₂ cells were selected in in vitro experiment and treated with different multiplicity of infection(MOI) (0,1,5,10,25 and 50) of pLXSN and pLXSN-Tum-5 virus particles for 72 h. The proliferation rates of cells in various groups were detected by MTT method.In vivo,the H22 tumor-bearing mouse models were established.The mice were divided into saline group,pLXSN group and pLXSN-Tum-5 group (n=5).The mice in saline group were intratumorally injected with normal saline,and the mice in pLXSN group and pLXSN-Tum-5 group were intratumorally injected with virus particles (MOI=5),5 times every other day.The volumes and weights of transplanted tumor and the weights of mice in various groups were measured.The CD31 expressions in transplanted tumor tissue were detected by immunohistochemical method and the microvessel density (MVD) was calculated. Results: Compared with pLXSN group,the proliferation rates of cells in pLXSN-Tum-5 group after infected with different MOI of virus particles were not significantly different (P> 0.05).The volumes and weights of transplanted tumor of the mice in pLXSN-Tum-5 group were significantly smaller than those in pLXSN group and saline group after intratumoral injection (P< 0.05 or P< 0.01).The immunohistochemical results showed that there was irregular angiogenesis in each group. Compared with saline group and pLXSN group,the mean value of MVD of the transplanted tumor tissue of the mice in pLXSN-Tum-5 group was significantly decreased (P< 0.05). Conclusion: Tum-5 can exert its antitumor activity by inhibiting the formation of neovascularization in HCC.

Key words: hepatocellular carcinoma, retroviral vector, tumstatin, angiogenesis