HDAC inhibitor trichostatin A suppresses esophageal squamous cell carcinoma metastasis through HADC2 reduced MMP-2/9.

Abstract

PURPOSE:

The histone deacetylase (HDAC) inhibitor trichostatin A (TSA) has been shown to act as an anti-tumor agent; however, the effect and mechanism of TSA on the invasion of esophageal squamous cell carcinoma (ESCC) remains unknown.

METHODS:

To determine whether TSA suppresses the invasiveness of ESCC cell via HDAC2, the expression of HDAC2 in ESCC tissues and adjacent non-tumor tissues were compared using Western blot and immunohistochemistry. Cells were transfected with HDAC2 siRNAs and non-targeting control siRNA using Lipofectamine TM 2000. Cell invasion was investigated using a transwell assay. The protein levels of matrix metalloproteinase-2/9 (MMP-2/9) were examined by Western blot analysis.

RESULTS:

Expression of HDAC2 was significantly higher in ESCC than in adjacent non-tumor tissues. Additionally, the in vitro invasion assay found that both downregulation of HDAC2 expression and TSA treatment inhibited ESCC cell invasion by approximately 75%. Also, an MMP2/9-specific inhibitor sharply suppressed ESCC cell invasion. Furthermore, both downregulation of HDAC2 and treatment with TSA decreased MMP-2 and MMP-9 protein levels in ESCC cells.

CONCLUSIONS:

These results suggest that the inhibitory effect of TSA on cancer invasion is mediated through the suppression of HDAC2 expression, and that the reduction of MMP-2 and MMP-9 expression induced by HDAC2 may be involved in the anti-invasive effect of TSA.

• Authors: Feng Wang, Yu Qi, Xin Li, Wei He, Qing-Xia Fan, Hong Zong
• Journal: Clinical and investigative medicine. Medecine clinique et experimentale (Clin Invest Med) Vol. 36 Issue 2 Pg. E87-94 (Apr 01 2013) ISSN: 1488-2353 [Electronic] Canada
• PMID: 23544610 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Histone Deacetylase Inhibitors
• Hydroxamic Acids
• RNA, Small Interfering
• trichostatin A
• MMP2 protein, human
• Matrix Metalloproteinase 2
• MMP9 protein, human
• Matrix Metalloproteinase 9
• Histone Deacetylase 2

Topics

• Antineoplastic Agents (pharmacology)
• Carcinoma, Squamous Cell (pathology)
• Cell Line, Tumor
• Esophageal Neoplasms (pathology)
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Histone Deacetylase 2 (metabolism)
• Histone Deacetylase Inhibitors (pharmacology)
• Humans
• Hydroxamic Acids (pharmacology)
• Matrix Metalloproteinase 2 (metabolism)
• Matrix Metalloproteinase 9 (metabolism)
• Neoplasm Invasiveness
• Neoplasm Metastasis
• RNA, Small Interfering (metabolism)