title: [Research on the effect and mechanism of polypeptide extract from scorpion venom combined with 5-fluorouracil on vasculogenic mimicry of H22 hepatoma].
abstract: OBJECTIVE
  To observe the inhibition effects of polypeptide extract from scorpion venom (PESV) combined 5-fluorouracil (5-Fu) on vasculogenic mimicry (VM) of H2 hepatoma carcinoma cells in mice and its possible mechanisms.
  
  
  METHODS
  The H22 carcinoma cell suspension was subcutaneously inoculated into 60 Kunming mice. Then tumor-bearing mice were randomly divided into three groups, i.e., the control group, the 5-Fu group, and the combination group (PESV +5-Fu), 20 in each group. The tumor volume was measured once every other day after 14 successive days of intervention. Then the tumor volume growth curve was drawn, and the tumor inhibitory rate was calculated. The morphological changes of the tumor tissue were observed by HE staining. The VM density of each tumor tissue were detected by immunohistochemical assay and periodic acid-schiff stain (PAS). The protein expression levels of hypoxia inducible factor-la (HIF-la) and matrix metalloproteinase-2 (MMP-2) were detected using immunohistochemical assay. The gray value was semi-quantitatively analyzed using LeicaQwinV3 Image Analysis Software.
  
  
  RESULTS
  The growth of H22 hepatoma transplantation tumor was inhibited more obviously in the combination group and the 5-Fu group than in the control group (P <0.05). There was statistical difference in the tumor weight and the tumor volume between the combination group and the 5-Fu group (P <0.05). Immunohistochemical assay and PAS showed that the VM density was obviously lower in the combination group than in the control group and the 5-Fu group (P <0.01). Compared with the control group, the protein expressions of HIF-la and MMP-2 significantly decreased in the combination group (P <0.01).
  
  
  CONCLUSIONS
  PESV combined 5-Fu could inhibit the generation of VM of H22 hepatoma transplantation tumor in mice. Its mechanisms might be associated with inhibiting the expressions of HIF-lalpha and MMP-2 in the microenvironment of tumors.
authors.affiliation: Department of Pathology, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Key Laboratory for Rare & Uncommon Diseases of Shandong Province, Jinan 250062, China
authors.forename: An-Hong
authors.initials: AH
authors.lastname: Zheng
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Zhang
authors.forename: Zhao-Peng
authors.initials: ZP
authors.lastname: Wang
authors.forename: Zhao-Xia
authors.initials: ZX
authors.lastname: Wang
authors.forename: Li-Cun
authors.initials: LC
authors.lastname: Wu
authors.forename: Qing
authors.initials: Q
authors.lastname: Jia
authors.forename: Yue-ying
authors.initials: YY
authors.lastname: Zhang
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000098:blood supply*; D045744:Cell Line, Tumor; D018999:Charybdotoxin / Q000494:pharmacology*; D005472:Fluorouracil / Q000494:pharmacology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008113:Liver Neoplasms / Q000098:blood supply*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains
chemical_list: C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D018999:Charybdotoxin; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse; D005472:Fluorouracil