title: Eupolyphaga sinensis Walker Ethanol Extract Suppresses Cell Growth and Invasion in Human Breast Cancer Cells.
abstract: OBJECTIVE
  To examine the antiproliferation and anti-invasion of Eupolyphaga sinensis Walker 70% ethanol extract (ESWE) on breast cancer and elucidate the underlying signaling mechanisms.
  
  
  METHODS
  MTT and colony formation assays were used to investigate the effect of ESWE on proliferation of breast cancer cells in vitro. The xenograft mouse tumor model was used to determine the effect of ESWE on breast cancer in vivo. To investigate the underlying molecular mechanisms, we used western blotting to analyze the expression of ERK1/2, CXCR4, matrix metalloproteinase 2 (MMP2), and MMP9 pretreated with ESWE. The stromal cell-derived factor (SDF)-1α-induced migration and invasion potential of breast cancer cells were examined by wound-healing assays and Matrigel invasion chamber assays.
  
  
  RESULTS
  ESWE effectively inhibited the proliferation of MDA-MB-435s and MDA-MB-231 cells and exhibited antitumor effects in an MDA-MB-231 xenograft mice model. Furthermore, ESWE suppressed the activity of ERK1/2, a key molecule of MAPK signaling. We also observed that ESWE treatment led to downregulation of CXCR4 expression as well as greatly reduced MMP2 and MMP9. ESWE affected CXCR4 expression partially through the modulation of autocrine vascular endothelial growth factor. However, suppression of CXCR4 expression was the result of downregulation of mRNA expression. Inhibition of CXCR4 expression by ESWE further correlated with the suppression of SDF-1α-induced migration and invasion in breast cancer cells.
  
  
  CONCLUSIONS
  ESWE exerted its antiproliferation and antiinvasion by regulating MAPK signaling and related metastasis factorsand thus could be a useful therapeutic candidate for breast cancer intervention.
authors.affiliation: Xi'an Jiaotong University, Xi'an, Shaanxi Province, P R China.
authors.forename: Yingzhuan
authors.initials: Y
authors.lastname: Zhan
authors.affiliation: Xi'an Jiaotong University, Xi'an, Shaanxi Province, P R China.
authors.forename: Han
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Xi'an Jiaotong University, Xi'an, Shaanxi Province, P R China.
authors.forename: Rui
authors.initials: R
authors.lastname: Liu
authors.affiliation: Xi'an Jiaotong University, Xi'an, Shaanxi Province, P R China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Wang
authors.affiliation: Xi'an Jiaotong University, Xi'an, Shaanxi Province, P R China.
authors.forename: Junpeng
authors.initials: J
authors.lastname: Qi
authors.affiliation: Xi'an Jiaotong University, Xi'an, Shaanxi Province, P R China zhang2008@mail.xjtu.edu.cn.
authors.forename: Yanmin
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001685:Biological Factors / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D003058:Cockroaches / Q000737:chemistry*; D000431:Ethanol / Q000737:chemistry*; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009361:Neoplasm Invasiveness / Q000517:prevention & control*; D019718:Receptors, CXCR4 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D001685:Biological Factors; C527276:CXCR4 protein, human; D019718:Receptors, CXCR4; D042461:Vascular Endothelial Growth Factor A; D000431:Ethanol; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
keywords: CXCR4; ERK1/2; Eupolyphaga sinensis Walker; MMP2; MMP9; breast cancer