title: Ginsenoside Rg3 enhances radiosensitization of hypoxic oesophageal cancer cell lines through vascular endothelial growth factor and hypoxia inducible factor 1α.
abstract: OBJECTIVE
  To determine if the pretreatment of hypoxic human oesophageal carcinoma cell lines (EC109, TE1 and KYSE170) with ginsenoside Rg3 (Rg3) increases their radiosensitivity to X-rays.
  
  
  METHODS
  The growth inhibitory effect of different Rg3 concentrations was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay. Radiation sensitivity was measured using a clone formation assay and flow cytometry was used to measure the effects of Rg3 on radiation-induced apoptosis. Western blot analysis was used to measure the effects of Rg3 on the levels of hypoxia inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF).
  
  
  RESULTS
  Rg3 inhibited EC109, TE1 and KYSE170 cell growth in a dose- and time-dependent manner. Pretreatment with 10 µmol/ml Rg3 increased EC109, TE1 and KYSE170 radiosensitivity. Rg3 plus radiation significantly increased the apoptosis rate compared with radiation alone. Rg3 also decreased VEGF and HIF-1α protein levels in EC109 cells in a dose-dependent manner. The combination of Rg3 and radiation increased the fragmentation of double-stranded DNA.
  
  
  CONCLUSIONS
  Rg3 enhanced the radiosensitivity of human oesophageal carcinoma cell lines cultured under hypoxic conditions possibly by downregulating VEGF and HIF-1α protein levels.
authors.affiliation: Department of Radiotherapy, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Ge
authors.affiliation: Department of Cardiothoracic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
authors.forename: Fuxi
authors.initials: F
authors.lastname: Zhen
authors.affiliation: Nantong Tumour Hospital, Nantong, Jiangsu Province, China.
authors.forename: Baixia
authors.initials: B
authors.lastname: Yang
authors.affiliation: Department of Radiotherapy, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Yang
authors.affiliation: Nantong Tumour Hospital, Nantong, Jiangsu Province, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Cai
authors.affiliation: Department of Radiotherapy, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
authors.forename: Chi
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Radiotherapy, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Radiotherapy, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
authors.forename: Yuandong
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Radiotherapy, Second People's Hospital of Lianyungang, Lianyungang, Jiangsu Province, China.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Synthetic Internal Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Cheng
authors.affiliation: Department of Radiotherapy, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China sunxinchen2012@163.com.
authors.forename: Xinchen
authors.initials: X
authors.lastname: Sun
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D004947:Esophagus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D015972:Gene Expression Regulation, Neoplastic; D036145:Ginsenosides / Q000494:pharmacology*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D011836:Radiation Tolerance; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D014965:X-Rays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D036145:Ginsenosides; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D011838:Radiation-Sensitizing Agents; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C097367:ginsenoside Rg3
keywords: Oesophageal carcinoma; ginsenoside Rg3; hypoxia inducible factor 1α; radiosensitizer; vascular endothelial growth factor