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Clin Invest Med. 2013 Apr 1;36(2):E87-94.

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

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1
Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, PR China.

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.

PMID:
23544610
[Indexed for MEDLINE]
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