title: Traditional Chinese medicine Jianpi Bushen therapy suppresses the onset of pre-metastatic niche in a murine model of spontaneous lung metastasis.
abstract: OBJECTIVE
  Distinct metastasis accounts for the leading cause of mortality among patients with gastric cancer. The formation of pre-metastatic niche in the target organs provides permissive environments for the adhesion and subsequent growth of metastasized cancer cells. Targeting the pre-metastatic niche is a potential approach to prevent metastasis. Traditional Chinese medicine regimen called Jianpi Bushen therapy (JPBS) has been widely used in clinics to strengthen patients' abilities to fight cancer. The present work is aimed to study the modulating effect of JPBS on the lungs expressions of Rac1, Cdc42, SDF-1, and FN in a murine gastric cancer model showing spontaneous lung metastasis.
  
  
  METHODS
  Mice of strain 615 were inoculated with tumor cells derived from mouse forestomach carcinoma (MFC) to induce spontaneous lung metastasis, and were then treated with JPBS, JPBS combined with fluorouracil (5-FU), or 5-FU. Gene and protein expressions of Rac1, Cdc42, SDF-1, and FN in lungs were determined using real-time PCR and immunohistochemistry, respectively. Serum levels of SDF-1 and FN were also measured using ELISA.
  
  
  RESULTS
  Gene and protein expressions of Rac1, Cdc42, SDF-1, and FN were significantly elevated in the lungs of model mice comparing to the counterpart mice received no tumor cell inoculation. JPBS treatment reduced protein expressions of Rac1, Cdc42, SDF-1 and FN in the lungs of model mice. The treatment could also suppress SDF-1 and FN in blood. For serum SDF-1 the level was further lower in model mice treated with combination therapy of JPBS and 5-FU.
  
  
  CONCLUSIONS
  The present work identified the potential roles of Rac1, Cdc42, SDF-1 and FN in the early onset of pre-metastatic niche of gastric cancer, and provided insights into the molecular mechanism by which Jianpi Bushen therapy prevent and suppress cancer metastasis.
authors.affiliation: Diabetes Laboratory, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Zhu
authors.affiliation: College of Acumox and Tuina, Beijing University of Chinese Medicine, Beijing 100029, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Pathology Laboratory, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China.
authors.forename: Qiu
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Department of Hematology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China. Electronic address: wujie150802@163.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Wu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D054377:Chemokine CXCL12 / Q000378:metabolism; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005472:Fluorouracil / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008516:Medicine, Chinese Traditional / Q000379:methods; D051379:Mice; D009362:Neoplasm Metastasis / Q000188:drug therapy*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: D054377:Chemokine CXCL12; D004365:Drugs, Chinese Herbal; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein; D005472:Fluorouracil
keywords: Gastric cancer; Jianpi Bushen therapy; Pre-metastatic niche