title: E2F-1 overexpression inhibits human gastric cancer MGC-803 cell growth in vivo.
abstract: OBJECTIVE
  To evaluate the influence of E2F-1 on the growth of human gastric cancer (GC) cells in vivo and the mechanism involved.
  
  
  METHODS
  E2F-1 recombinant lentiviral vectors were injected into xenograft tumors of MGC-803 cells in nude mice, and then tumor growth was investigated. Overexpression of transcription factor E2F-1 was assessed by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting analysis. Apoptosis rates were determined using a terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay. Expression levels of certain cell cycle regulators and apoptosis-related proteins, such as Bax, survivin, Bcl-2, cyclin D1, S-phase kinase-associated protein 2, and c-Myc were examined by Western blotting and RT-PCR.
  
  
  RESULTS
  Xenograft tumors of MGC-803 cells in nude mice injected with E2F-1 recombinant lentiviral vectors stably overexpressed the E2F-1 gene as measured by semi-quantitative RT-PCR (relative mRNA expression: 0.10 ± 0.02 vs 0.05 ± 0.02 for control vector and 0.06 ± 0.03 for no infection; both P < 0.01) and Western blotting (relative protein expression: 1.90 ± 0.05 vs 1.10 ± 0.03 in control vector infected and 1.11 ± 0.02 for no infection; both P < 0.01). The growth-curve of tumor volumes revealed that infection with E2F-1 recombinant lentiviral vectors significantly inhibited the growth of human GC xenografts (2.81 ± 1.02 vs 6.18 ± 1.15 in control vector infected and 5.87 ± 1.23 with no infection; both P < 0.05) at 15 d after treatment. TUNEL analysis demonstrated that E2F-1 overexpression promoted tumor cell apoptosis (18.6% ± 2.3% vs 6.7% ± 1.2% in control vector infected 6.3% ± 1.2% for no infection; both P < 0.05). Furthermore, lentiviral vector-mediated E2F-1 overexpression increased the expression of Bax and suppressed survivin, Bcl-2, cyclin D1, Skp2, and c-Myc expression in tumor tissue.
  
  
  CONCLUSIONS
  E2F-1 inhibits growth of GC cells via regulating multiple signaling pathways, and may play an important role in targeted therapy for GC.
authors.affiliation: Wei-Yuan Wei, Lin-Hai Yan, Wen-Long Cao, Xiao-Shi Zhang, Ze-Xu Zhan, Han Yu, Qiang Xiao, Department of Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
authors.forename: Wei-Yuan
authors.initials: WY
authors.lastname: Wei
authors.affiliation: Wei-Yuan Wei, Lin-Hai Yan, Wen-Long Cao, Xiao-Shi Zhang, Ze-Xu Zhan, Han Yu, Qiang Xiao, Department of Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
authors.forename: Lin-Hai
authors.initials: LH
authors.lastname: Yan
authors.affiliation: Wei-Yuan Wei, Lin-Hai Yan, Wen-Long Cao, Xiao-Shi Zhang, Ze-Xu Zhan, Han Yu, Qiang Xiao, Department of Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
authors.forename: Xiao-Tong
authors.initials: XT
authors.lastname: Wang
authors.affiliation: Wei-Yuan Wei, Lin-Hai Yan, Wen-Long Cao, Xiao-Shi Zhang, Ze-Xu Zhan, Han Yu, Qiang Xiao, Department of Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.affiliation: Wei-Yuan Wei, Lin-Hai Yan, Wen-Long Cao, Xiao-Shi Zhang, Ze-Xu Zhan, Han Yu, Qiang Xiao, Department of Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
authors.forename: Wen-Long
authors.initials: WL
authors.lastname: Cao
authors.affiliation: Wei-Yuan Wei, Lin-Hai Yan, Wen-Long Cao, Xiao-Shi Zhang, Ze-Xu Zhan, Han Yu, Qiang Xiao, Department of Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
authors.forename: Xiao-Shi
authors.initials: XS
authors.lastname: Zhang
authors.affiliation: Wei-Yuan Wei, Lin-Hai Yan, Wen-Long Cao, Xiao-Shi Zhang, Ze-Xu Zhan, Han Yu, Qiang Xiao, Department of Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
authors.forename: Ze-Xu
authors.initials: ZX
authors.lastname: Zhan
authors.affiliation: Wei-Yuan Wei, Lin-Hai Yan, Wen-Long Cao, Xiao-Shi Zhang, Ze-Xu Zhan, Han Yu, Qiang Xiao, Department of Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
authors.forename: Han
authors.initials: H
authors.lastname: Yu
authors.affiliation: Wei-Yuan Wei, Lin-Hai Yan, Wen-Long Cao, Xiao-Shi Zhang, Ze-Xu Zhan, Han Yu, Qiang Xiao, Department of Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
authors.forename: Yu-Bo
authors.initials: YB
authors.lastname: Xie
authors.affiliation: Wei-Yuan Wei, Lin-Hai Yan, Wen-Long Cao, Xiao-Shi Zhang, Ze-Xu Zhan, Han Yu, Qiang Xiao, Department of Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xiao
mesh_terms: D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D050687:E2F1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden; D015854:Up-Regulation
chemical_list: D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D012333:RNA, Messenger
keywords: E2F-1; Gastric cancer; Lentiviral vector; Mouse model