title: [Inhibitory effect of migration-inducing gene-7-shRNA recombinant retrovirus combined with endostatin on growth and metastasis of hepatoma xenograft].
abstract: Objective:To investigate the inhibitory effect of migration-inducing gene-7(Mig-7)interfered with retrovirus-mediated RNA(shRNA)combined with recombinant human endostatin(ES)on the growth and metastasis of subcutaneous xenograft of human hepatoma cells in nude mice.Methods:Two Mig-7-mRNA oligonucleotide sequences(Mig-7-shRNA-1 and Mig-7-shRNA-2)and one sequence as a negative control(Mig-7-shRNA-N)were designed. The specific Mig-7-shRNA recombinant retrovirus expression vector plasmid was constructed and used for the transfection of human hepatoma MHCC-97H cells with high expression of Mig-7. The subcutaneous xenograft tumor model of human hepatocellular carcinoma(HCC)in nude mice was established, and according to the condition of transfection and administration, the nude mice were divided into pSIREN-M1 group, pSIREN-MN group, ES group, and pSIREN-M1+ES group. The xenograft tumor volume, mass, and metastasis were compared between groups. Immunohistochemistry was used to observe the formation of vasculogenic mimicry(VM)in xenograft tumor and the difference in tumor microvascular density(MVD), and Western blot was used to measure the expression of Mig-7 and vascular endothelial growth factor(VEGF)in each group. A one-way analysis of variance was used for comparison between groups, and the Fisher's exact test was used for comparison of continuous data between groups.Results:Compared with the pSIREN-MN group, the pSIREN-M1 group had significantly lower xenograft tumor volume, mass, and metastasis rate, Mig-7 expression, and formation of VM(P< 0.05), as well as significantly higher VEGF expression and MVD(P< 0.05). Compared with the pSIREN-MN group, the ES group had significantly lower xenograft tumor volume, mass, and metastasis rate, VEGF expression, and MVD(P< 0.05), as well as significantly higher Mig-7 expression and formation of VM(P< 0.05). Compared with the pSIREN-M1 group and the ES group, the pSIREN-M1+ES group had significantly lower xenograft tumor volume, mass, and metastasis rate, Mig-7 expression, formation of VM, VEGF expression, and MVD(P< 0.05).Conclusion:Mig-7-shRNA recombinant retrovirus combined with ES has a better inhibitory effect on the growth and metastasis of HCC xenograft tumor than Mig-7-shRNA recombinant retrovirus or ES alone. The anti-tumor angiogenesis therapy alone, which targets vascular endothelial cells in vivo, has a limited effect, since it may promote the formation of VM.
authors: Department of General Surgery, Affiliated Hospital of Logistics University of Chinese People's Armed Police Forces, Tianjin 300162, China.
authors: B
authors: B
authors: Qu
authors: Department of General Surgery, Postgraduate Training Basement of Jinzhou Medical University, Affiliated Hospital of Logistics University of Chinese People's Armed Police Forces, Tianjin 300162, China.
authors: G N
authors: GN
authors: Chen
authors: Department of General Surgery, Postgraduate Training Basement of Jinzhou Medical University, Affiliated Hospital of Logistics University of Chinese People's Armed Police Forces, Tianjin 300162, China.
authors: G N
authors: GN
authors: Sheng
authors: Department of General Surgery, Postgraduate Training Basement of Jinzhou Medical University, Affiliated Hospital of Logistics University of Chinese People's Armed Police Forces, Tianjin 300162, China.
authors: F
authors: F
authors: Yu
authors: Institute of Medical Rescue, Affiliated Hospital of Logistics University of Chinese People's Armed Police Forces, Tianjin 300162, China.
authors: Q
authors: Q
authors: Lyu
authors: Department of Pathology, Affiliated Hospital of Logistics University of Chinese People's Armed Police Forces, Tianjin 300162, China.
authors: Y J
authors: YJ
authors: Gu
authors: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
authors: L
authors: L
authors: Guo
authors: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
authors: Y
authors: Y
authors: Lyu
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular; D045744:Cell Line, Tumor; D043169:Endostatins; D005822:Genetic Vectors; D064593:Heterografts; D006801:Humans; D008113:Liver Neoplasms; D051379:Mice; D008819:Mice, Nude; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D012190:Retroviridae / Q000235:genetics*; D014162:Transfection; D047368:Tumor Burden; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: D043169:Endostatins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A