[Effect of HDAC6 down-regulation on the growth of xenografted human laryngeal carcinoma cell line Hep-2 in nude mice and underlying mechanism]

Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2012 Jun;47(6):481-6.
[Article in Chinese]

Abstract

Objective: To study the effect of histone deacetylation 6 (HDAC6) siRNA on the growth of xenografted human laryngeal squamous cell carcinoma cell line Hep-2 in nude mice and underlying mechanism.

Methods: Laryngeal squamous cell carcinoma cell line Hep-2 cells were subcutaneously injected to the back of nude mice and transplanted tumor model was established after one week. Nude mice was divided into three groups including blank control group, empty vector group and HDAC6 siRNA group, and the tumor growth was observed. Ki-67 proliferation index was detected by immunohistochemistry. Western blot, in situ hybridization and immunohistochemistry were used to detect the mRNA and protein expressions of HDAC6 in xenograft. The expressions of Bcl-2 and Bax proteins were examined by Western blotting. Cell apoptosis was detected by TUNEL.

Results: The mean volume of xenograft transfected with HDAC6 siRNA was less than that of xenograft transfected with empty vector or that of xenograft with blank control treatment (P < 0.05). HDAC6 siRNA effectively down-regulated the expressions of HDAC6 mRNA and the expressions of HDAC6 and Bcl-2 proteins, but up-regulated the expression of Bcl-2 protein in xenografts, with significant differences (all P < 0.05). The proliferation index of Ki-67 in HDAC6 siRNA transfection group was significantly lower than that in blank control group or empty vector group (P < 0.05). TUNEL assay demonstrated that HDAC6 evidently evoked cell apoptosis (P < 0.05).

Conclusion: HDAC6 siRNA could effectively inhibited the growth of xenografted human laryngeal carcinoma cell line Hep-2 in nude mice, down-regulate the expressions of HDAC6 and bcl-2, and up-regulate the expression of bax.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Down-Regulation
  • Female
  • Histone Deacetylase 6
  • Histone Deacetylases / genetics
  • Histone Deacetylases / metabolism*
  • Humans
  • Laryngeal Neoplasms / metabolism*
  • Laryngeal Neoplasms / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger / genetics
  • RNA, Small Interfering / genetics
  • Transfection
  • Xenograft Model Antitumor Assays
  • bcl-2-Associated X Protein / metabolism

Substances

  • Bax protein, mouse
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • RNA, Small Interfering
  • bcl-2-Associated X Protein
  • Bcl2 protein, mouse
  • Hdac6 protein, mouse
  • Histone Deacetylase 6
  • Histone Deacetylases