title: Tumor-specific expression of shVEGF and suicide gene as a novel strategy for esophageal cancer therapy.
abstract: OBJECTIVE
  To develop a potent and safe gene therapy for esophageal cancer.
  
  
  METHODS
  An expression vector carrying fusion suicide gene (yCDglyTK) and shRNA against vascular endothelial growth factor (VEGF) was constructed and delivered into EC9706 esophageal cancer cells by calcium phosphate nanoparticles (CPNP). To achieve tumor selectivity, expression of the fusion suicide gene was driven by a tumor-specific human telomerase reverse transcriptase (hTERT) promoter. The biologic properties and therapeutic efficiency of the vector, in the presence of prodrug 5-fluorocytosine (5-FC), were evaluated in vitro and in vivo.
  
  
  RESULTS
  Both in vitro and in vivo testing showed that the expression vector was efficiently introduced by CPNP into tumor cells, leading to cellular expression of yCDglyTK and decreased VEGF level. With exposure to 5-FC, it exhibited strong anti-tumor effects against esophageal cancer. Combination of VEGF shRNA with the fusion suicide gene demonstrated strong anti-tumor activity.
  
  
  CONCLUSIONS
  The shVEGF-hTERT-yCDglyTK/5-FC system provided a novel approach for esophageal cancer-targeted gene therapy.
authors.affiliation: Ting Liu, Ya-Qi Chen, Ai-Min Leng, Wei-Jian Yuan, Gui-Ying Zhang, Jie Peng, Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Liu
authors.affiliation: Ting Liu, Ya-Qi Chen, Ai-Min Leng, Wei-Jian Yuan, Gui-Ying Zhang, Jie Peng, Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China.
authors.forename: Hai-Jun
authors.initials: HJ
authors.lastname: Wu
authors.affiliation: Ting Liu, Ya-Qi Chen, Ai-Min Leng, Wei-Jian Yuan, Gui-Ying Zhang, Jie Peng, Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Ting Liu, Ya-Qi Chen, Ai-Min Leng, Wei-Jian Yuan, Gui-Ying Zhang, Jie Peng, Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China.
authors.forename: Xu-Jun
authors.initials: XJ
authors.lastname: Liang
authors.affiliation: Ting Liu, Ya-Qi Chen, Ai-Min Leng, Wei-Jian Yuan, Gui-Ying Zhang, Jie Peng, Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China.
authors.forename: Hui-Chao
authors.initials: HC
authors.lastname: Huang
authors.affiliation: Ting Liu, Ya-Qi Chen, Ai-Min Leng, Wei-Jian Yuan, Gui-Ying Zhang, Jie Peng, Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China.
authors.forename: Yan-Zhong
authors.initials: YZ
authors.lastname: Zhao
authors.affiliation: Ting Liu, Ya-Qi Chen, Ai-Min Leng, Wei-Jian Yuan, Gui-Ying Zhang, Jie Peng, Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China.
authors.forename: Qing-Chuan
authors.initials: QC
authors.lastname: Liao
authors.affiliation: Ting Liu, Ya-Qi Chen, Ai-Min Leng, Wei-Jian Yuan, Gui-Ying Zhang, Jie Peng, Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China.
authors.forename: Ya-Qi
authors.initials: YQ
authors.lastname: Chen
authors.affiliation: Ting Liu, Ya-Qi Chen, Ai-Min Leng, Wei-Jian Yuan, Gui-Ying Zhang, Jie Peng, Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China.
authors.forename: Ai-Min
authors.initials: AM
authors.lastname: Leng
authors.affiliation: Ting Liu, Ya-Qi Chen, Ai-Min Leng, Wei-Jian Yuan, Gui-Ying Zhang, Jie Peng, Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China.
authors.forename: Wei-Jian
authors.initials: WJ
authors.lastname: Yuan
authors.affiliation: Ting Liu, Ya-Qi Chen, Ai-Min Leng, Wei-Jian Yuan, Gui-Ying Zhang, Jie Peng, Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China.
authors.forename: Gui-Ying
authors.initials: GY
authors.lastname: Zhang
authors.affiliation: Ting Liu, Ya-Qi Chen, Ai-Min Leng, Wei-Jian Yuan, Gui-Ying Zhang, Jie Peng, Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Peng
authors.affiliation: Ting Liu, Ya-Qi Chen, Ai-Min Leng, Wei-Jian Yuan, Gui-Ying Zhang, Jie Peng, Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China.
authors.forename: Yong-Heng
authors.initials: YH
authors.lastname: Chen
mesh_terms: D000818:Animals; D002130:Calcium Phosphates / Q000737:chemistry; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry; D004938:Esophageal Neoplasms / Q000628:therapy*; D005260:Female; D005437:Flucytosine / Q000008:administration & dosage / Q000627:therapeutic use; D041722:Genes, Transgenic, Suicide; D005822:Genetic Vectors / Q000008:administration & dosage*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D000067492:RNAi Therapeutics / Q000379:methods*; D019098:Telomerase / Q000235:genetics; D014162:Transfection; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D002130:Calcium Phosphates; D004337:Drug Carriers; D034741:RNA, Small Interfering; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; C020243:calcium phosphate; D005437:Flucytosine; C509186:TERT protein, human; D019098:Telomerase
keywords: Esophageal cancer; Nanoparticles; RNA interference; Suicide gene; Vascular endothelial growth factor