title: Lentivirus-mediated RNA interference targeting E2F-1 inhibits human gastric cancer MGC-803 cell growth in vivo.
abstract: The E2F-1 transcription factor is post-translationally modified and stabilized in response to various forms of DNA damage to regulate the expression of cell-cycle and pro-apoptotic genes. The sustained overexpression of E2F-1 is a characteristic feature of gastric cancer. In this study, we investigated the role of short hairpin RNA (shRNA) targeting E2F-1 gene on human gastric cancer MGC-803 cell growth in vivo, and preliminarily revealed the mechanism. Thus, we constructed recombinant pGCSIL-GFP-shRNA-E2F-1 lentiviral vector to knock down E2F-1 expression in human gastric cancer MGC-803 cells in vivo, and studied the effect of E2F-1 shRNA on growth of MGC-803 tumor and evaluated its treatment efficacy. Our data demonstrated that in a mouse model of established gastric cancer, intratumor injection of lentiviral shRNA targeting E2F-1 definitely decreased the endogenous E2F-1 mRNA and protein expression in MGC-803 tumor, and inhibited tumor growth and promoted tumor cells apoptosis. Moreover, we found that E2F-1 shRNA increased the expression of phosphatase and tensin homolog (PTEN), activated caspase-3 and caspase-9, and suppressed nuclear factor (NF)-κB expression in tumor tissue as determined by reverse transcription (RT)-PCR and western blotting. In summary, shRNA targeting of E2F-1 can effectively inhibits human gastric cancer MGC-803 cell growth in vivo and may be a potential therapeutic strategy for gastric cancer.
authors.affiliation: Department of Surgery, The First Affiliated Hospital Guangxi Medical University Nanning 530021, China.
authors.forename: Xiao Tong
authors.initials: XT
authors.lastname: Wang
authors.forename: Yu Bo
authors.initials: YB
authors.lastname: Xie
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xiao
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002478:Cells, Cultured; D050687:E2F1 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005822:Genetic Vectors / Q000008:administration & dosage; D006801:Humans; D016086:Lentivirus / Q000235:genetics*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control*
chemical_list: D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D034741:RNA, Small Interfering; D053148:Caspase 3; D053453:Caspase 9