title: BDE-99 (2,2',4,4',5-pentabromodiphenyl ether) triggers epithelial-mesenchymal transition in colorectal cancer cells via PI3K/Akt/Snail signaling pathway.
abstract: OBJECTIVE
  The gut is in direct contact with BDE-99 (2,2',4,4',5-pentabromodiphenyl ether), one of the most abundant PBDE congeners in the environment and in human tissues. The objective of the present study was to investigate the effects of BDE-99 on colorectal cancer (CRC) cells.
  
  
  METHODS
  The effects of BDE-99 on cell proliferation were measured by CCK-8 assay in the CRC cell line HCT-116. Wound healing and transwell migration/invasion assays were used to test the migration and invasion of CRC cells. Factors related to epithelial-to-mesenchymal transition (EMT) were measured by real-time PCR and Western blot analysis for mRNA and protein levels, respectively.
  
  
  RESULTS
  BDE-99 was found to increase migration and invasion and trigger EMT in HCT-116 cells; EMT was characterized by cells acquiring mesenchymal spindle-like morphology and by increased expression of N-cadherin with a concomitant decrease in E-cadherin. BDE-99 treatment also increased the protein and mRNA levels of the transcription factor Snail, but not Slug, Twist, and ZEB1. Knockdown of Snail by siRNA significantly attenuated BDE-99-induced EMT in HCT-116 cells, suggesting that Snail plays a crucial role in BDE-99-induced EMT. The PI3K/Akt inhibitor LY294002 completely blocked BDE-99-induced Snail and invasion of HCT-116 cells.
  
  
  CONCLUSIONS
  Our results revealed that BDE-99 can trigger the EMT of colon cancer cells via the PI3K/AKT/Snail signaling pathway. This study provides new insight into the tumorigenesis and metastasis of CRC stimulated by BDE-99 and possibly other PBDE congeners.
authors.affiliation: Medical Oncology, Beijing Military General Hospital, Beijing - China.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.forename: Xin-Jian
authors.initials: XJ
authors.lastname: Ruan
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Zhang
mesh_terms: D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D045325:HCT116 Cells; D055768:Halogenated Diphenyl Ethers / Q000009:adverse effects*; D006801:Humans; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects / Q000378:metabolism*; D034622:RNA Interference / Q000187:drug effects; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000187:drug effects / Q000378:metabolism*; D014945:Wound Healing
chemical_list: C477694:2,2',4,4',5-brominated diphenyl ether; D055768:Halogenated Diphenyl Ethers; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt