title: Adenovirus-mediated expression of p33(ING1b) induces apoptosis and inhibits proliferation in gastric adenocarcinoma cells in vitro.
abstract: BACKGROUND
  Inhibitor of growth 1b (ING1b) is considered to be a class II tumor suppressor gene. Although reduced expression of p33(ING1b) has been reported in many human malignancies, including gastric cancers, the effect of p33(ING1b) on gastric cancer cells has yet to be investigated.
  
  
  METHODS
  Expression of p33(ING1b) in gastric adenocarcinoma tissues and their adjacent non-malignant gastric mucosa, as well as in gastric adenocarcinoma cell lines and normal gastric epithelial cells, was detected by using Western blotting. Recombinant adenoviruses were prepared to mediate the ectopic expression of p33(ING1b) (Ad-ING1b) and green fluorescent protein (GFP)(Ad-GFP) in the gastric adenocarcinoma cell lines, SGC-7901, MKN28, and MKN45 and the normal gastric epithelial cell line GES-1. Alterations in the proliferation and apoptosis of the cells after adenoviral infection were determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry, respectively, and cell cycle distribution was analyzed in a fluorescence-activated cell sorter.
  
  
  RESULTS
  Western blotting confirmed the reduced expression of p33(ING1b) in gastric adenocarcinoma tissues and gastric adenocarcinoma cell lines. The ectopic expression of p33(ING1b) mediated by Ad-ING1b resulted in decreased growth, increased apoptosis, and cell cycle arrest at the G1 phase in both benign and malignant gastric epithelial cells regardless of their p53 status. Addition of a p53 inhibitor, pifithrin-α, did not abolish the pro-apoptotic and cell cycle-arresting effects of p33(ING1b) in p53 wild-type cells.
  
  
  CONCLUSIONS
  Down-regulation of p33(ING1b) might play an important role in the development of gastric adenocarcinoma. Targeted local expression of p33(ING1b) may offer a promising alternative therapeutic measure for gastric cancer.
authors.affiliation: Department of Gastroenterology, 1st Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, 710061 Xi'an, China.
authors.forename: Yifei
authors.initials: Y
authors.lastname: Lv
authors.forename: Bibek Kumar
authors.initials: BK
authors.lastname: Purbey
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Huang
authors.forename: Shuang
authors.initials: S
authors.lastname: Li
authors.forename: Gurung
authors.initials: G
authors.lastname: Radha
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Hao
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000256:Adenoviridae / Q000235:genetics*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D052160:Benzothiazoles / Q000494:pharmacology; D045744:Cell Line, Tumor; D015536:Down-Regulation; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014050:Toluene / Q000031:analogs & derivatives / Q000494:pharmacology; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D052160:Benzothiazoles; C501503:ING1 protein, human; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D011994:Recombinant Proteins; D025521:Tumor Suppressor Proteins; D014050:Toluene; C121565:pifithrin