title: [Inhibition of human laryngeal carcinoma growth by gene therapy and epigenetic therapy].
abstract: OBJECTIVE
  To observe the effects of gene therapy and epigenetic therapy on the tumor growth of laryngeal carcinoma and the underlying mechanisms.
  
  
  METHODS
  The animal model of human laryngeal carcinoma was established by the subcutaneous inoculation of Hep-2 cells at the right armpit of BALB/c nu/nu mice. The tumor-bearing mice were randomized into 4 groups, p53 therapy group(rAd-p53), epigenetic therapy group(5-aza-dC), combination therapy group (rAd-p53+5-aza-dC) and control group. The gene and protein expressions of molecular markers p53 and E-cadherin were detected by FQ-PCR and immunohistochemistry.
  
  
  RESULTS
  By the day 20 of the treatments, the mean tumor volumes were(106.09 ± 24.40)mm(3) in p53 therapy group, (166.55 ± 40.11) mm(3) in epigenetic therapy group, (126.11 ± 22.49) mm(3) in combination therapy group,and (252.83 ± 54.09) mm(3) in control group. Both gene therapy (F = 37.30, P < 0.05) and epigenetic therapy (F = 4.79, P < 0.05) inhibited the growth of xenografted tumors, with an interaction effect (F = 22.01, P < 0.05) between the two groups. The integral optical density value of p53 protein expression of p53 therapy group (628.07 ± 95.16) was significantly higher than that of combination therapy group (494.76 ± 100.22), (t = 8.72, P < 0.05). The integral optical density values of E-cadherin protein expression were 558.89 ± 97.58 in p53 therapy group, 380.41 ± 90.60 in epigenetic therapy group, 494.76 ± 102.88 in combination therapy group,and 162.60 ± 40.38 in control group respectively, indicating the enhancements of E-cadherin protein expression by gene therapy (F = 45.24, P < 0.05) or epigenetic therapy(F = 5.73, P < 0.05)and the existence of interaction effect (F = 21.82, P < 0.05) between gene therapy and epigenetic therapy. The expression levels of p53 gene were 4.43 ± 0.12 in p53 therapy group, 1.06 ± 0.11 in epigenetic therapy group, 3.51 ± 0.10 in combination therapy group,and 1.09 ± 0.11 in control group, respectively, showing an interaction effect between gene therapy and epigenetic therapy (F = 298.11, P < 0.05). The expression levels of E-cadherin gene were 4.50 ± 0.34 in p53 therapy group, 2.02 ± 0.16 in epigenetic therapy group, 2.99 ± 0.12 in combination therapy group, and 1.00 ± 0.11 in control group, respectively. The expression of E-cadherin gene was enhanced by gene therapy (F = 329.12, P < 0.05)or epigenetic therapy(F = 88.57, P < 0.05), with an interaction effect between the two therapies (F = 122.17, P < 0.05).
  
  
  CONCLUSIONS
  Xenografted tumors of human laryngeal carcinoma cells are inhibited by gene therapy, the epigenetic therapy and the combination therapy. The gene therapy was significantly better than the epigenetic therapy or the combination therapy. There might be antagonistic effect between p53 and 5-aza-dC.
authors.affiliation: Department of Otorhinolaryngology Head and Neck Surgery, Capital Medical University, Beijing, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Lian
authors.forename: Ling-yan
authors.initials: LY
authors.lastname: Jiang
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Er-zhong
authors.initials: EZ
authors.lastname: Fan
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.forename: Ju-gao
authors.initials: JG
authors.lastname: Fang
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002277:Carcinoma / Q000628:therapy*; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D057890:Epigenomics; D015316:Genetic Therapy; D006801:Humans; D007822:Laryngeal Neoplasms / Q000628:therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D015820:Cadherins; D016159:Tumor Suppressor Protein p53