title: Effect of YangZheng XiaoJi Extract, DME-25, on Endothelial Cells and their Response to Avastin.
abstract: BACKGROUND
  Angiogenesis is a cellular process that has been identified as a key target for therapy in solid cancer. However, over the course of anti-angiogenic therapies, cancer cells acquire resistance to these therapies after an initial period of success. DME-25 is an extract from Yang Zheng Xiao Ji, a traditional Chinese medicine that has been reported to benefit patients with cancer by alleviating chemotherapy-associated symptoms and possibly inhibiting key cancer cell traits. This study aimed to explore if DME-25 on its own and in combination with avastin affected endothelial cell behaviour in vitro in the presence of hypoxic lung cancer-conditioned medium (CM).
  
  
  METHODS
  Two lung cancer cell lines, A549 and SK-MES-1, were exposed to hypoxic conditions (O2 ≤1%) for 4 h, after which CM, and RNA were collected. Transcript expression of several influential angiogenic markers in lung cancer cells were assessed following hypoxic/normoxic conditions. Lung cancer CM was added in combination with avastin and DME-25, before or after vascular endothelial growth factor (VEGF) depletion, to endothelial cells (HECV) and cell migration and microtubule formation were assessed in vitro.
  
  
  RESULTS
  HECV cell migration was reduced in the presence of avastin, although less efficiently in the presence of lung cancer CM. A combination of DME-25 and avastin with lung cancer CM significantly reduced HECV cell migration irrespective of culture under hypoxia or normoxia. Depletion of VEGF from the CM reduced the inhibitory capacity of avastin, however, it appeared to have little impact on the anti-angiogenic effects of DME-25.
  
  
  CONCLUSIONS
  DME-25 inhibits tubule formation irrespectively of the factors secreted by normoxic or hypoxic lung cancer cell CM depleted of VEGF.
authors.affiliation: Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Cardiff, U.K. Cardiff University-Capital Medical University Joint Centre for BioMedical Research and Cancer Institute, Capital Medical University, Beijing, P.R. China.
authors.forename: Sioned
authors.initials: S
authors.lastname: Owen
authors.affiliation: Yiling Medical Research Institute, ShijiaZhuang, HeBei Province, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Cardiff University-Capital Medical University Joint Centre for BioMedical Research and Cancer Institute, Capital Medical University, Beijing, P.R. China Department of Thoracic Surgery, Beijing XuanWu Hospital, Capital Medical University, Beijing, P.R. China Beijing Lung Cancer Centre, Capital Medical University, Beijing, P.R. China.
authors.forename: Xiuyi
authors.initials: X
authors.lastname: Zhi
authors.affiliation: Yiling Medical Research Institute, ShijiaZhuang, HeBei Province, P.R. China.
authors.forename: Cong
authors.initials: C
authors.lastname: Wei
authors.affiliation: Yiling Medical Research Institute, ShijiaZhuang, HeBei Province, P.R. China.
authors.forename: Yiling
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Cardiff, U.K. Cardiff University-Capital Medical University Joint Centre for BioMedical Research and Cancer Institute, Capital Medical University, Beijing, P.R. China Beijing Lung Cancer Centre, Capital Medical University, Beijing, P.R. China jiangw@cardiff.ac.uk.
authors.forename: Wen G
authors.initials: WG
authors.lastname: Jiang
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D000068258:Bevacizumab / Q000494:pharmacology*; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D019899:Paracrine Communication / Q000187:drug effects; D013997:Time Factors; D059016:Tumor Microenvironment; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D017077:Culture Media, Conditioned; D004365:Drugs, Chinese Herbal; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C579032:yangzheng xiaoji; D000068258:Bevacizumab
keywords: DME-25; Lung cancer; avastin; endothelial cells; hypoxia; traditional Chinese medicine