Inhibition of human laryngeal carcinoma growth by gene therapy and epigenetic therapy / 中华耳鼻咽喉头颈外科杂志

ABSTRACT

<p><b>OBJECTIVE</b>To observe the effects of gene therapy and epigenetic therapy on the tumor growth of laryngeal carcinoma and the underlying mechanisms.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSIONS</b>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.</p>