title: Enhanced proliferation, invasion, and epithelial-mesenchymal transition of nicotine-promoted gastric cancer by periostin.
abstract: OBJECTIVE
  To investigate the contribution of periostin in nicotine-promoted gastric cancer cell proliferation, survival, invasion, drug resistance, and epithelial-mesenchymal transition (EMT).
  
  
  METHODS
  Gastric cancer cells were treated with nicotine and periostin protein expression was determined by immunoblotting. Periostin mRNA in gastric cancer cells was silenced using small interfering RNA (siRNA) techniques and periostin gene expression was evaluated by quantitative reverse transcription-polymerase chain reaction. Gastric cancer cells transfected with control or periostin siRNA plasmid were compared in terms of cell proliferation using the methylthiazolyldiphenyl-tetrazolium bromide assay. Cell apoptosis was compared using annexin V-fluoresceine isothiocyanate and propidium iodine double staining. Tumor invasion was determined using the Boyden chamber invasion assay, and the EMT marker Snail expression was evaluated by immunoblotting.
  
  
  RESULTS
  Nicotine upregulated periostin in gastric cancer cells through a COX-2 dependent pathway, which was blocked by the COX-2-specific inhibitor NS398. Periostin mRNA expression was decreased by ~87.2% by siRNA in gastric cancer cells, and stable periostin-silenced cells were obtained by G418 screening. Periostin-silenced gastric cancer cells exhibited reduced cell proliferation, elevated sensitivity to chemotherapy with 5-fluorouracil, and decreased cell invasion and Snail expression (P < 0.05).
  
  
  CONCLUSIONS
  Periostin is a nicotine target gene in gastric cancer and plays a role in gastric cancer cell growth, invasion, drug resistance, and EMT facilitated by nicotine.
authors.affiliation: Division of Basic Medicine, Department of Pathology, Central South University Xiangya School of Medicine, Changsha 410 013, Hunan Province, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.forename: Bao-An
authors.initials: BA
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D054337:Cell Dedifferentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D009361:Neoplasm Invasiveness; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology; D009578:Nitrobenzenes / Q000494:pharmacology; D034622:RNA Interference; D000071250:Snail Family Transcription Factors; D013274:Stomach Neoplasms / Q000139:chemically induced* / Q000473:pathology* / Q000503:physiopathology; D013449:Sulfonamides / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; D052246:Cyclooxygenase 2 Inhibitors; D018722:Nicotinic Agonists; D009578:Nitrobenzenes; C512835:POSTN protein, human; D000071250:Snail Family Transcription Factors; D013449:Sulfonamides; D014157:Transcription Factors; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D009538:Nicotine; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human