title: Adenovirus-mediated delivery of interferon-γ gene inhibits the growth of nasopharyngeal carcinoma.
abstract: BACKGROUND
  Interferon-γ (IFN-γ) is regarded as a potent antitumor agent, but its clinical application is limited by its short half-life and significant side effects. In this paper, we tried to develop IFN-γ gene therapy by a replication defective adenovirus encoding the human IFN-γ (Ad-IFNγ), and evaluate the antitumoral effects of Ad-IFNγ on nasopharyngeal carcinoma (NPC) cell lines in vitro and in xenografts model.
  
  
  METHODS
  The mRNA levels of human IFN-γ in Ad-IFNγ-infected NPC cells were detected by reverse transcription-polymerase chain reaction (RT-PCR), and IFN-γ protein concentrations were measured by enzyme-linked immunosorbent assay (ELISA) in the culture supernatants of NPC cells and tumor tissues and bloods of nude mice treated with Ad-IFNγ. The effects of Ad-IFNγ on NPC cell proliferation was determined using MTT assay, cell cycle distribution was determined by flow cytometry analysis for DNA content, and cells apoptosis were analyzed by Annexin V-FITC/7-AAD binding assay and hoechst 33342/PI double staining. The anti-tumor effects and toxicity of Ad-IFNγ were evaluated in BALB/c nude mice carrying NPC xenografts.
  
  
  RESULTS
  The results demonstrated that Ad-IFNγ efficiently expressed human IFN-γ protein in NPC cell lines in vitro and in vivo. Ad-IFNγ infection resulted in antiproliferative effects on NPC cells by inducing G1 phase arrest and cell apoptosis. Intratumoral administration of Ad-IFNγ significantly inhibited the growth of CNE-2 and C666-1 cell xenografts in nude mice, while no significant toxicity was observed.
  
  
  CONCLUSIONS
  These findings indicate IFN-γ gene therapy mediated by replication defective adenoviral vector is likely a promising approach in the treatment of nasopharyngeal carcinoma.
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, 651 Dong-feng Road East, Guangzhou, 510060, China.
authors.forename: Ran-yi
authors.initials: RY
authors.lastname: Liu
authors.forename: Ying-hui
authors.initials: YH
authors.lastname: Zhu
authors.forename: Ling
authors.initials: L
authors.lastname: Zhou
authors.forename: Peng
authors.initials: P
authors.lastname: Zhao
authors.forename: Hong-li
authors.initials: HL
authors.lastname: Li
authors.forename: Lan-cai
authors.initials: LC
authors.lastname: Zhu
authors.forename: Hong-yu
authors.initials: HY
authors.lastname: Han
authors.forename: Huan-xin
authors.initials: HX
authors.lastname: Lin
authors.forename: Liang
authors.initials: L
authors.lastname: Kang
authors.forename: Jiang-xue
authors.initials: JX
authors.lastname: Wu
authors.forename: Wenlin
authors.initials: W
authors.lastname: Huang
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D017209:Apoptosis; D002277:Carcinoma; D049109:Cell Proliferation; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics* / Q000627:therapeutic use*; D051379:Mice; D008819:Mice, Nude; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000473:pathology* / Q000628:therapy*; D023041:Xenograft Model Antitumor Assays
chemical_list: D007371:Interferon-gamma