title: Helicobacter pylori promotes apoptosis, activates cyclooxygenase (COX)-2 and inhibits heat shock protein HSP70 in gastric cancer epithelial cells.
abstract: OBJECTIVE
  Apoptosis plays an important role in the regulation of gastric epithelial cell number and gastrointestinal disorders induced by Helicobacter pylori (Hp). Heat shock proteins (HSPs) are involved in cell integrity, cell growth and in gastric mucosa colonized by Hp. COX-2 was implicated in Hp-induced carcinogenesis but the effects of this germ and CagA cytotoxin on HSP70, COX-2, Bax and Bcl-2 in gastric cancer epithelial cells have been little studied.
  
  
  METHODS
  We determined the expression for HSP70, Bax and Bcl-2 in human gastric epithelial MKN7 cells incubated with live strain Hp (cagA + vacA+) with or without co-incubation with exogenous CagA and NS-398, the selective COX-2 inhibitor. After 3-48 h of incubation, the expression of HSP70, COX-2, Bax and Bcl-2 mRNA and proteins were determined by RT-PCR and immunoprecipitation.
  
  
  RESULTS
  Hp inhibited expression for HSP70 and this was significantly potentiated by exogenous CagA. Co-incubation of epithelial cells with Hp, without or with CagA increased Bax expression and simultaneously decreased expression for Bcl-2. The increase in COX-2 mRNA and Bax expression were significantly inhibited by NS-398. We conclude that Hp promotes apoptosis in adenocarcinoma gastric epithelial cells in vitro and this is associated with activation of COX-2 and inhibition of HSP70.
authors.affiliation: Department of Physiology, Jagiellonian University Medical College, 16 Grzegorzecka Str., 31-531, Cracow, Poland.
authors.forename: Aneta
authors.initials: A
authors.lastname: Targosz
authors.forename: Tomasz
authors.initials: T
authors.lastname: Brzozowski
authors.forename: Piotr
authors.initials: P
authors.lastname: Pierzchalski
authors.forename: Urszula
authors.initials: U
authors.lastname: Szczyrk
authors.forename: Agata
authors.initials: A
authors.lastname: Ptak-Belowska
authors.forename: Stanislaw Jan
authors.initials: SJ
authors.lastname: Konturek
authors.forename: Wieslaw
authors.initials: W
authors.lastname: Pawlik
mesh_terms: D000942:Antigens, Bacterial / Q000494:pharmacology; D017209:Apoptosis; D001426:Bacterial Proteins / Q000494:pharmacology; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016480:Helicobacter pylori; D006801:Humans; D009578:Nitrobenzenes / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013274:Stomach Neoplasms / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000942:Antigens, Bacterial; C494826:BAX protein, human; D001426:Bacterial Proteins; D016861:Cyclooxygenase Inhibitors; D018840:HSP70 Heat-Shock Proteins; D009578:Nitrobenzenes; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D013449:Sulfonamides; C074689:VacA protein, Helicobacter pylori; D051028:bcl-2-Associated X Protein; C080866:cagA protein, Helicobacter pylori; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human