title: Astragaloside IV inhibits breast cancer cell invasion by suppressing Vav3 mediated Rac1/MAPK signaling.
abstract: BACKGROUND
  Astragaloside IV (AS-IV), the major active triterpenoid in Radix Astragali, has shown anti-tumorigenic properties in certain cancers; however, its role in breast cancer remains unclear. The present study investigated the effects of AS-IV on breast cancer in vitro and in vivo and examined the underlying mechanisms.
  
  
  METHODS
  The effects of AS-IV on MDA-MB-231 cell proliferation, migration, invasion and metastasis were investigated by MTT and Transwell assays, and western blotting. In addition, an orthotopic mouse tumor model was established for in vivo experiments.
  
  
  RESULTS
  AS-IV inhibited the viability and invasive potential of MDA-MB-231 breast cancer cells, suppressed the activation of the mitogen activated protein kinase (MAPK) family members ERK1/2 and JNK, and downregulated matrix metalloproteases (MMP)-2 and -9. The effects of AS-IV were mediated by the downregulation of Vav3, a guanine nucleotide exchange factor, leading to decreased levels of activated Rac1, a Rho family GTPase. Vav3 overexpression promoted cell proliferation and invasion in vitro, whereas Vav3 silencing had the opposite effects. AS-IV suppressed orthotopic breast tumor growth and metastasis to the lungs, whereas ectopic expression of Vav3 reversed the inhibitory effect of AS-IV on cell viability, invasiveness, MAPK signaling and MMP expression.
  
  
  CONCLUSIONS
  The present results provide a mechanistic explanation for the antitumor effects of AS-IV and suggest its potential in the treatment of metastatic breast cancer.
authors.affiliation: Department of Breast Diseases, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, 110 Ganhe Rd, Shanghai, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Jiang
authors.affiliation: Department of Breast Diseases, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, 110 Ganhe Rd, Shanghai, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Lu
authors.affiliation: Department of Breast Diseases, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, 110 Ganhe Rd, Shanghai, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Breast Diseases, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, 110 Ganhe Rd, Shanghai, China.
authors.forename: Yajie
authors.initials: Y
authors.lastname: Ji
authors.affiliation: Department of Breast Diseases, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, 110 Ganhe Rd, Shanghai, China.
authors.forename: Weili
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Breast Diseases, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, 110 Ganhe Rd, Shanghai, China. Electronic address: xiaohong_xue@126.com.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Xue
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D027885:Astragalus propinquus; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004365:Drugs, Chinese Herbal; D048049:Extracellular Signal-Regulated MAP Kinases; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D051567:Proto-Oncogene Proteins c-vav / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D012503:Saponins / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D014315:Triterpenes / Q000494:pharmacology*; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D004365:Drugs, Chinese Herbal; D051567:Proto-Oncogene Proteins c-vav; C107953:RAC1 protein, human; D034741:RNA, Small Interfering; D012503:Saponins; D014315:Triterpenes; C496621:VAV3 protein, human; C052064:astragaloside A; C027492:Huang Qi; D048049:Extracellular Signal-Regulated MAP Kinases; D020830:rac1 GTP-Binding Protein
keywords: Astragaloside IV; Breast cancer cells; Rac1/MAPK signaling; Vav3