title: Gensenoside Rg3 inhibits hypoxia-induced VEGF expression in human cancer cells.
abstract: OBJECTIVE
  The ginsenoside Rg3 (Rg3) inhibits xenograft growth and angiogenesis in tumors mainly via down-regulates VEGF expression. This study was designed to investigate the mechanisms by which Rg3 down-regulates VEGF expression.
  
  
  METHODS
  MTT assay was performed to investigate the effect of Rg3 on the growth of human esophageal carcinoma cell line Eca-109 and 786-0 cells under normoxic and hypoxic conditions. ELISA was used to detect VEGF protein secreted by the cells under normoxic and hypoxic conditions. Real-time quantitative reverse transcriptase polymerase chain reaction and Western blotting were used to detect gene expression and protein synthesis.
  
  
  RESULTS
  Rg3 inhibited Eca-109 and 786-0 cell proliferation and induced a significant reduction in VEGF mRNA under hypoxia conditions. Rg3 treatment inhibited hypoxia-induced expression HIF-1α, COX-2 and NF-κB under normoxic and hypoxic conditions. Treatment with Rg3 reduced the hypoxia-induced phosphorylation of STAT3 in a dose-dependent manner in the both cell lines. Rg3 treatment also inhibited the phosphorylation of ERK1/2 and JNK induced by hypoxia.
  
  
  CONCLUSIONS
  Rg3 targets hypoxia-induced multiple signaling pathways to down-regulate VEGF expression in cancer cells. These actions may contribute to the overall efficacy of Rg3 against tumor angiogenesis and growth.
authors.affiliation: Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou City.
authors.forename: Qing-Jiang
authors.initials: QJ
authors.lastname: Chen
authors.forename: Ming-Zhi
authors.initials: MZ
authors.lastname: Zhang
authors.forename: Le-Xin
authors.initials: LX
authors.lastname: Wang
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D051546:Cyclooxygenase 2 / Q000378:metabolism; D036145:Ginsenosides / Q000494:pharmacology*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
chemical_list: D020533:Angiogenesis Inhibitors; D036145:Ginsenosides; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016328:NF-kappa B; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; D042461:Vascular Endothelial Growth Factor A; C097367:ginsenoside Rg3; D051546:Cyclooxygenase 2; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3