title: [Anti-tumor effect of eukaryotic expressing plasmid containing soluble tumor necrotic factor-related apoptosis inducing ligand combined with human angiostatin Kringle (1 - 3) genes on human gastric cancer xenografts in nude mice].
abstract: OBJECTIVE
  To investigate the anti-tumor effect of eukaryotic expressing plasmid containing human angiostatin Kringle (1 - 3) [hAG (K1-3)] combined with soluble tumor necrotic factor-related apoptosis inducing ligand (sTRAIL) genes on human gastric cancer xenografts in nude mice.
  
  
  METHODS
  Recombinant plasmids of pBud-hAG and pBud-hAG-TRAIL were constructed by subcloning technique. Twenty nude BALB/c mice were inoculated with human gastric cancer cells of the line BGC-823 subcutaneously into the back. One week later after the appearance of implanted tumors the mice were randomly divided into 4 groups with pBud-hAG, pBud-hAG-TRAIL, pBud blank plasmid, and normal saline (NS) injected into the tumors respectively once the other day for 7 times. The size of tumor was observed. 7 days later the mice were killed with their tumors taken out. RT-PCR was used to detect the expression of hAG and sTRAIL. The microvessel density (MVD) of tumor was observed and recorded by detecting the protein of CD34 with immunohistochemistry on the microscopy.
  
  
  RESULTS
  The MVD of tumor in the pBud-hAG-TRAIL and pBud-hAG groups were (4.8 +/- 0.9)/HP and (4.6 +/- 1.2)/HP respectively, significantly lower than those of the pBud and NS groups [(17.4 +/- 2.4)/HP and (18.2 +/- 2.7)/HP respectively, all P < 0.05], but there was no significant difference between the pBud-hAG-TRAIL and pBud-hAG groups. mRNA expression and protein expression of sTRAIL and hAG were positive in the pBud-hAG-TRAIL and pBud-hAG groups. The tumor volumes of tumors of the pBud-hAG-TRAIL and pBud-hAG groups were (1.325 +/- 0.012) cm(3) and (1.862 +/- 0.017) cm(3) respectively, both significantly lower than those of the pBud and NS groups [(3.637 +/- 0.032) cm(3) and (3.521 +/- 0.028) cm(3) respectively, all P < 0.05].
  
  
  CONCLUSIONS
  Angiostatin inhibits tumor angiogenesis through inhibiting the growth of vascular endothelial cells, and TRAIL induces tumor cell apoptosis. hAG (K1-3) combined with TRAIL can inhibit tumor growth more efficiently.
authors: Infection Institute of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors: Wei
authors: W
authors: Sun
authors: Zheng
authors: Z
authors: Jiang
authors: Ting-Xiu
authors: TX
authors: Xiang
authors: Xiao-Hong
authors: XH
authors: Tao
authors: Ai-Long
authors: AL
authors: Huang
authors: Pi-Long
authors: PL
authors: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D045744:Cell Line, Tumor; D005260:Female; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009389:Neovascularization, Pathologic; D010446:Peptide Fragments / Q000235:genetics*; D010958:Plasminogen / Q000235:genetics*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
chemical_list: D010446:Peptide Fragments; D053221:TNF-Related Apoptosis-Inducing Ligand; C402400:recombinant kringle 1-3 (rKI-3) of human plasminogen; D010958:Plasminogen