Valproic acid inhibit non-small-cell lung cancer (A549 cell line) metastasis via inhibition of CD44v6 and Nm23H1
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Currently, epigenetic changes are considered to be one of the most important factors in the incidence of cancer and its metastasis to various tissues. It has been shown that CD44v6 and Nm23-H1 genes play a crucial role in the metastasis of various cancers. However, no study has been done on the effect of epigenetic factors on the expression of CD44v6 and Nm23-H1 genes in the lung cancer cell line, A549.Therefore, the present study investigated the role of a histone deacetylase inhibitor, valproic acid, on the expression of CD44v6 and Nm23-H1 genes and proteins in the A549 cell line. In this study, the A549 cell line was treated with valproic acid at concentrations of 2.2 mM, 4.5 mM, and 9 mM. We then investigated the expression of CD44v6 and Nm23-H1 genes and proteins, as well as the expression of MMP-2 and MMP-9 genes and caspase-3 activity. The results showed that valproic acid significantly decreased the expression of CD44v6 gene and protein and MMP-2 and MMP-9 genes, but increased the expression of Nm23H1 gene and protein and the activity of caspase-3 (p˂ 0.05). Our results showed that histone deacetylases affected the expression of CD44v6, Nm23-H1, MMP-2, and MMP-9, which are involved in metastasis. Therefore, the use of histone deacetylase inhibitors can be effective in the suppression of metastases and the treatment of lung cancer.
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