title: [The effect of RhoA and proteasome inhibitor MG132 on angiogenesis in tumors].
abstract: OBJECTIVE
  To investigate the effect of RhoA to VEGF, HIF-1alpha and MVD (microvascular density) and the effect of MG132 to RhoA.
  
  
  METHODS
  The constitutively-active mutant vectors of RhoA (pCEFL-GST-V14RhoA) were transfected into gastric cancer cell line MKN-45 by Lipofectamine 2000, single clones were selected by G418 and identified with western blot. The content of VEGF in the conditioned media was detected by ELISA. Constitutively-active RhoA nude mice models were established and treated with MG132. The effect of RhoA and MG132 on expression of HIF-1alpha, VEGF and CD31 were detected by immunohistochemistry.
  
  
  RESULTS
  Cell line of stable-transfected constitutively-active RhoA was established and constitutively-active RhoA could stimulate secretion of VEGF but MG132 inhibited that. Constitutively-active RhoA could obviously induce growth of tumor (P < 0.05), but MG132 inhibited it (P < 0.05). Constitutively-active RhoA could promote protein of HIF-1alpha, VEGF and CD31 but MG132 inhibited the function of RhoA (P < 0.05).
  
  
  CONCLUSIONS
  Our studies indicates that MG132 could affect angiogenesis of tumors through inhibition the regulating function of RhoA on HIF-1alpha, VEGF and CD31.
authors.affiliation: Laboratory of Signal Transduction & Molecular Targeted Therapy, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Cai-Xia
authors.initials: CX
authors.lastname: Yue
authors.forename: Ji
authors.initials: J
authors.lastname: Ma
authors.forename: Hai-Jun
authors.initials: HJ
authors.lastname: Zhou
authors.forename: Qiu-Lin
authors.initials: QL
authors.lastname: Tang
authors.forename: Li-Lan
authors.initials: LL
authors.lastname: Li
authors.forename: Feng
authors.initials: F
authors.lastname: Bi
authors.forename: Yan
authors.initials: Y
authors.lastname: Xue
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D045744:Cell Line, Tumor; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007976:Leupeptins / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D061988:Proteasome Inhibitors; D013274:Stomach Neoplasms / Q000098:blood supply* / Q000473:pathology; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000037:antagonists & inhibitors* / Q000494:pharmacology
chemical_list: D020533:Angiogenesis Inhibitors; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007976:Leupeptins; D061988:Proteasome Inhibitors; D042461:Vascular Endothelial Growth Factor A; C066737:RHOA protein, human; D020742:rhoA GTP-Binding Protein; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde