title: Acetylcholinesterase overexpression mediated by oncolytic adenovirus exhibited potent anti-tumor effect.
abstract: BACKGROUND
  Acetylcholinesterase (AChE) mainly functions as an efficient terminator for acetylcholine signaling transmission. Here, we reported the effect of AChE on gastric cancer therapy.
  
  
  METHODS
  The expression of AChE in gastric cancerous tissues and adjacent non-cancerous tissues was examined by immunohistochemistry. Gastric cancer cells were treated with AChE delivered by replication-deficient adenoviral vector (Ad.AChE) or oncolytic adenoviral vector (ZD55-AChE), respectively, followed by measurement of cell viability and apoptosis by MTT assay and apoptosis detection assays. In vivo, the tumor growth of gastric cancer xenografts in mice treated with Ad.AChE or ZD55-AChE (1  × 10(9) PFU) were measured. In addition, the cell viability of gastric cancer stem cells treated with Ad.AChE or ZD55-AChE were evaluated by MTT assay.
  
  
  RESULTS
  A positive correlation was found between higher level of AChE expression in gastric cancer patient samples and longer survival time of the patients. Ad.AChE and ZD55-AChE inhibited gastric cancer cell growth, and low dose of ZD55-AChE induced mitochondrial pathway of apoptosis in cells. ZD55-AChE repressed tumor growth in vivo, and the anti-tumor efficacy is greater than Ad.AChE. Moreover, ZD55-AChE suppressed the growth of gastric cancer stem cells.
  
  
  CONCLUSIONS
  ZD55-AChE represented potential therapeutic effect for human gastric cancer.
authors.forename: Haineng
authors.initials: H
authors.lastname: Xu
authors.forename: Zhengxuan
authors.initials: Z
authors.lastname: Shen
authors.forename: Jing
authors.initials: J
authors.lastname: Xiao
authors.forename: Yu
authors.initials: Y
authors.lastname: Yang
authors.forename: Weidan
authors.initials: W
authors.lastname: Huang
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Zhou
authors.forename: Jiani
authors.initials: J
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China. zhuyz@fudan.edu.cn.
authors.forename: Yizhun
authors.initials: Y
authors.lastname: Zhu
authors.forename: Xin-Yuan
authors.initials: XY
authors.lastname: Liu
authors.forename: Liang
authors.initials: L
authors.lastname: Chu
mesh_terms: D000110:Acetylcholinesterase / Q000235:genetics / Q000378:metabolism*; D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D005822:Genetic Vectors / Q000008:administration & dosage; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D050130:Oncolytic Virotherapy / Q000379:methods*; D013274:Stomach Neoplasms / Q000473:pathology / Q000628:therapy*; D016019:Survival Analysis; D023041:Xenograft Model Antitumor Assays
chemical_list: D000110:Acetylcholinesterase