title: Anti-tumour effects of small interfering RNA targeting anion exchanger 1 in experimental gastric cancer.
abstract: OBJECTIVE
  Anion exchanger 1 (AE1) is an integral membrane protein found in erythrocytes. Our previous studies have demonstrated that AE1 is expressed in human gastric cancer cells and may be involved in the carcinogenesis of cancer. In this study, we further investigated the role of AE1 in gastric carcinogenesis and the anti-tumour effects of AE1-targeted small interfering RNAs (siRNAs) in two experimental models of gastric cancer.
  
  
  METHODS
  Molecular and cellular experiments were performed to elucidate the role of AE1 in the malignant transformation of gastric epithelium and the effects of AE1-targeted siRNAs on gastric cancer cells. The anti-tumour effect of the siRNA was evaluated in vivo in two mouse models, nude mice implanted with human gastric cancer xenografts (Model I) and mice with gastric cancer induced by N-methyl-N-nitrosourea (MNU) and Helicobacter pylori (Model II).
  
  
  RESULTS
  AE1 was found to increase gastric carcinogenesis by promoting cell proliferation. AE1-targeted siRNA significantly suppressed AE1 expression and hindered tumour growth. Furthermore, the siRNA markedly decreased the detection rate of gastric cancer, in parallel with an increase in atypical hyperplasia at the end of the experiment in Model II.
  
  
  CONCLUSIONS
  Knockdown of AE1 expression in gastric mucosa by administration of synthetic siRNAs significantly inhibits the growth of gastric cancer and decreases the detection rate of this tumour in experimental mice. These results suggest that AE1 is potentially a key therapeutic target and the silencing of AE1 expression in gastric mucosa could provide a new therapeutic approach for treating gastric cancer.
authors.affiliation: Department of Pathology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Wen-Hao
authors.initials: WH
authors.lastname: Suo
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.forename: Ping-Ping
authors.initials: PP
authors.lastname: Wu
authors.forename: Lei
authors.initials: L
authors.lastname: Zhao
authors.forename: Ling-Jun
authors.initials: LJ
authors.lastname: Song
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Shen
authors.forename: Lin
authors.initials: L
authors.lastname: Zheng
authors.forename: Jing
authors.initials: J
authors.lastname: Tao
authors.forename: Xi-Dai
authors.initials: XD
authors.lastname: Long
authors.forename: Guo-Hui
authors.initials: GH
authors.lastname: Fu
mesh_terms: D000818:Animals; D001457:Anion Exchange Protein 1, Erythrocyte / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D005260:Female; D055785:Gene Knockdown Techniques; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000628:therapy*; D034741:RNA, Small Interfering; D013274:Stomach Neoplasms / Q000139:chemically induced / Q000628:therapy*
chemical_list: D001457:Anion Exchange Protein 1, Erythrocyte; D034741:RNA, Small Interfering