title: YangZheng XiaoJi exerts anti-tumour growth effects by antagonising the effects of HGF and its receptor, cMET, in human lung cancer cells.
abstract: BACKGROUND
  Hepatocyte growth factor (HGF) is a cytokine that has a profound effect on cancer cells by stimulating migration and invasion and acting as an angiogenic factor. In lung cancer, the factor also plays a pivotal role and is linked to a poor outcome in patients. In particular, HGF is known to work in combination with EGF on lung cancer cells. In the present study, we investigated the effect of a traditional Chinese medicine reported in cancer therapies, namely YangZheng XiaoJi (YZXJ) on lung cancer and on HGF mediated migration and invasion of lung cancer cells.
  
  
  METHODS
  Human lung cancer cells, SKMES1 and A549 were used in the study. An extract from the medicine was used. Cell migration was investigated using the EVOS and by ECIS. Cell-matrix adhesion and in vitro invasion were assessed. In vivo growth of lung cancer was tested using an in vivo xenograft tumour model and activation of the HGF receptor in lung tumours by an immunofluorescence method.
  
  
  RESULTS
  Both lung cancer cells increased their migration in response to HGF and responded to YZXJ by reducing their speed of migration. YZXJ markedly reduced the migration and in vitro invasiveness induced by HGF. It worked synergistically with PHA665752 and SU11274, HGF receptor inhibitors on the lung cancer cells both on HGF receptor activation and on cell functions. A combination of HGF and EGF resulted in a greater increase in cell migration, which was similarly inhibited by YZXJ, and in combination with the HGF receptor and EGF receptor inhibitors. In vivo, YZXJ reduced the rate of tumour growth and potentiated the effects of PHA665752 on tumour growth. It was further revealed that YZXJ significantly reduced the degree of phosphorylation of the HGF receptor in lung tumours.
  
  
  CONCLUSIONS
  YZXJ has a significant role in reducing the migration, invasion and in vivo tumour growth of lung cancer and acts to inhibit the migratory and invasive effects induced by HGF and indeed by HGF/EGF. This effect is likely attributed to the inhibition of the HGF receptor activation. These results indicate that YZXJ has a therapeutic role in lung cancer and that combined strategy with methods to block HGF and EGF should be considered.
authors: Cardiff University-Peking University Cancer Institute, Cardiff University School of Medicine, Henry Wellcome Building, Heath Park, Cardiff, CF14 4XN, UK. jiangw@cf.ac.uk.
authors: Wen G
authors: WG
authors: Jiang
authors: Cardiff University-Peking University Cancer Institute, Cardiff University School of Medicine, Henry Wellcome Building, Heath Park, Cardiff, CF14 4XN, UK. YeL@cf.ac.uk.
authors: Lin
authors: L
authors: Ye
authors: Cardiff University-Peking University Cancer Institute, Cardiff University School of Medicine, Henry Wellcome Building, Heath Park, Cardiff, CF14 4XN, UK. Ruge@cf.ac.uk.
authors: Fiona
authors: F
authors: Ruge
authors: Cardiff University-Peking University Cancer Institute, Cardiff University School of Medicine, Henry Wellcome Building, Heath Park, Cardiff, CF14 4XN, UK. OwenS15@cf.ac.uk.
authors: Sioned
authors: S
authors: Owen
authors: Cardiff University-Peking University Cancer Institute, Cardiff University School of Medicine, Henry Wellcome Building, Heath Park, Cardiff, CF14 4XN, UK. MartinTA1@cf.ac.uk.
authors: Tracey
authors: T
authors: Martin
authors: Cardiff University-Peking University Cancer Institute, Cardiff University School of Medicine, Henry Wellcome Building, Heath Park, Cardiff, CF14 4XN, UK. SunP2iangw@cf.ac.uk.
authors: Ping-Hui
authors: PH
authors: Sun
authors: Cardiff University-Peking University Cancer Institute, Cardiff University School of Medicine, Henry Wellcome Building, Heath Park, Cardiff, CF14 4XN, UK. SandersAJ1@cf.ac.uk.
authors: Andrew J
authors: AJ
authors: Sanders
authors: Cardiff University-Peking University Cancer Institute, Cardiff University School of Medicine, Henry Wellcome Building, Heath Park, Cardiff, CF14 4XN, UK. LaneJ1@cf.ac.uk.
authors: Jane
authors: J
authors: Lane
authors: Cardiff University-Peking University Cancer Institute, Cardiff University School of Medicine, Henry Wellcome Building, Heath Park, Cardiff, CF14 4XN, UK. SatherleyLK2@cf.ac.uk.
authors: Lucy
authors: L
authors: Satherley
authors: Cardiff University-Peking University Cancer Institute, Cardiff University School of Medicine, Henry Wellcome Building, Heath Park, Cardiff, CF14 4XN, UK. JimH@cf.ac.uk.
authors: Hoi P
authors: HP
authors: Weeks
authors: Yiling Medical Research Institute, No. 238 TianShan DaJie, Shijianzhuang, HeBei Province, China. GaoYong@Yiling.cn.
authors: Yong
authors: Y
authors: Gao
authors: Yiling Medical Research Institute, No. 238 TianShan DaJie, Shijianzhuang, HeBei Province, China. WeiCong@Yiling.cn.
authors: Cong
authors: C
authors: Wei
authors: Yiling Medical Research Institute, No. 238 TianShan DaJie, Shijianzhuang, HeBei Province, China. Yilingwu@Yiling.cn.
authors: Yiling
authors: Y
authors: Wu
authors: Cardiff University-Peking University Cancer Institute, Cardiff University School of Medicine, Henry Wellcome Building, Heath Park, Cardiff, CF14 4XN, UK. MasonMD@cf.ac.uk.
authors: Malcolm D
authors: MD
authors: Mason
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D016207:Cytokines / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000737:chemistry*; D017097:Electric Impedance; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D017228:Hepatocyte Growth Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D008175:Lung Neoplasms / Q000378:metabolism*; D008516:Medicine, Chinese Traditional; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D018919:Neovascularization, Physiologic; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; D016207:Cytokines; D004365:Drugs, Chinese Herbal; C066855:HGF protein, human; D011994:Recombinant Proteins; C579032:yangzheng xiaoji; D017228:Hepatocyte Growth Factor; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met