title: A Chinese herbal formula, Yi-Qi-Fu-Sheng, inhibits migration/invasion of colorectal cancer by down-regulating MMP-2/9 via inhibiting the activation of ERK/MAPK signaling pathways.
abstract: BACKGROUND
  A Chinese herbal formula, Yi-Qi-Fu-Sheng (YQFS), has long been employed clinically to treat cancer patients. We aimed to determine its effectiveness as a treatment method for colorectal cancer. We investigated the therapeutic effects of YQFS on colorectal cancer, as well as the underlying mechanisms, which have not previously been explored.
  
  
  METHODS
  First, YQFS was extracted and chemically characterized. We then tested the effects of YQFS on proliferation and migration by MTT and transwell migration assays in vitro. Mouse xenograft models of colorectal cancer were established by inoculation with HCT-116 cells, and mice received one of three oral doses (200, 400 and 800 mg/kg/day) to evaluate the effects of YQFS extract. Metalloproteinase-2/9 (MMP-2/9) expression in mice was evaluated by gelatin zymography assay. Apoptosis was evaluated by flow cytometry (FCM) analysis in vitro and by TUNEL assay in vivo. ERK and p-ERK expression were evaluated by western blot analysis at the protein level in vitro, and by quantitative RT-PCR at mRNA level in vivo.
  
  
  RESULTS
  Our results show that YQFS significantly inhibits colorectal cancer cell proliferation and induces apoptosis and cell cycle arrest at the G1- and S-phase in HCT-116 cells. Furthermore, YQFS effectively retards tumor cell migration and invasion by inhibiting metalloproteinase-2/9 (MMP-2/9) expression, both in vitro and in vivo. Moreover, YQFS had an inhibitory effect on tumor growth in vivo, and induced apoptosis through the inhibition of the ERK1/2 pathway both in vitro and in vivo.
  
  
  CONCLUSIONS
  These findings demonstrate that YQFS extract has an anti-tumor effect in colorectal cancer, which could be attributed to ERK1/2-dependent inhibition of MMP-2/9 expression.
authors.affiliation: Oncology Department I of Traditional Chinese Medical Hospital of Xinjiang Uygur Autonomous Region, Xinjiang 830000, China. dengwanwan7723@sina.com
authors.forename: Wanli
authors.initials: W
authors.lastname: Deng
authors.forename: Hua
authors.initials: H
authors.lastname: Sui
authors.forename: Qiaolin
authors.initials: Q
authors.lastname: Wang
authors.forename: Nana
authors.initials: N
authors.lastname: He
authors.forename: Chunyan
authors.initials: C
authors.lastname: Duan
authors.forename: Liang
authors.initials: L
authors.lastname: Han
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
authors.forename: Ming
authors.initials: M
authors.lastname: Lu
authors.forename: Shuqin
authors.initials: S
authors.lastname: Lv
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D015536:Down-Regulation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9