Down-regulation of matrix-invasive potential of human liver cancer cells by type I interferon and a histone deacetylase inhibitor sodium butyrate.
Down-regulation of matrix-invasive potential of human liver cancer cells by type I interferon and a histone deacetylase inhibitor sodium butyrate.
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DOI：
10.3892/ijo.24.4.837
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发表时间：
2004-04
影响因子：
5.2
通讯作者：
F. Kaneko;H. Saito;Yoshimasa Saito;K. Wakabayashi;N. Nakamoto;S. Tada;Hidekazu Suzuki;S. Tsunematsu;N. Kumagai;H. Ishii
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文献类型：
--
作者：
F. Kaneko;H. Saito;Yoshimasa Saito;K. Wakabayashi;N. Nakamoto;S. Tada;Hidekazu Suzuki;S. Tsunematsu;N. Kumagai;H. Ishii
我们已经证明干扰素-α 和组蛋白脱乙酰酶抑制剂丁酸钠对人肝癌细胞系具有抗增殖和抗转移作用。在本研究中，检测了人肝癌细胞系通过基质包被膜的侵袭能力，并研究了干扰素-α和丁酸钠的抑制作用。使用 Matrigel 侵袭试验，在 6 种人类肝癌细胞系中，HLE 和 HLF 显示出高侵袭能力。用1000 IU/ml的干扰素-α或2 mM的丁酸钠预处理细胞可显着抑制这种侵袭能力。明胶酶谱和基质金属蛋白酶-2和-9活性测定表明，这两种细胞系产生活性基质金属蛋白酶-2和-9，并且用两种试剂预处理后其活性显着降低。实时定量逆转录聚合酶链式反应显示，两种药物预处理后基质金属蛋白酶-1 mRNA 水平均有所降低，但干扰素-α 和丁酸钠对基质金属蛋白酶-1 和-2 组织抑制剂的 mRNA 水平有不同的调节。这些结果表明，干扰素-α和丁酸钠通过抑制基质金属蛋白酶活性来减少人肝癌细胞侵袭和转移的机会，尽管其抑制剂的调节不同。
We have demonstrated anti-proliferation and anti-metastasis effects of both interferon-alpha and a histone deacetylase inhibitor, sodium butyrate, on human liver cancer cell lines. In this study, invasive ability of human liver cancer cell lines through the matrix-coated membrane was examined and inhibitory effect of interferon-alpha and sodium butyrate was investigated. Among six human liver cancer cell lines, HLE and HLF showed high invasive ability using the Matrigel invasion assay. This invasion ability was significantly inhibited by pretreatment of the cells with 1000 IU/ml of interferon-alpha or 2 mM of sodium butyrate. Gelatin zymography and the matrix metalloproteinase-2 and -9 activity assay showed that these two cell lines produce active- and pro-matrix metalloproteinase-2 and -9, and their activity was significantly reduced by pretreatment with both agents. Real-time quantitative reverse transcription-polymerase chain reaction showed decrease in matrix metalloproteinase-1 mRNA levels by pretreatment with both agents, but mRNA levels of tissue inhibitor of matrix metalloproteinase-1 and -2 were differently modulated by interferon-alpha and sodium butyrate. These results suggest that interferon-alpha and sodium butyrate reduce a chance of invasion and metastasis of human liver cancer cells by inhibiting matrix metalloproteinase activity, although its inhibitor is differently regulated.