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Extracellular matrix degradation by matrix metalloproteinases (<jats:styled-content style=\"fixed-case\">MMP<\/jats:styled-content>s) has been connected with cancer cell invasion, and it has been suggested that inhibition of <jats:styled-content style=\"fixed-case\">MMP<\/jats:styled-content>s by synthetic and natural inhibitors may be of great importance in the <jats:styled-content style=\"fixed-case\">HCC<\/jats:styled-content> therapies. Melatonin, the main product of the pineal gland, exerts antiproliferative, proapoptotic, and antiangiogenic properties in <jats:styled-content style=\"fixed-case\">H<\/jats:styled-content>ep<jats:styled-content style=\"fixed-case\">G<\/jats:styled-content>2 human hepatocellular cells, and exhibits anti\u2010invasive and antimetastatic activities by suppressing the enzymatic activity of <jats:styled-content style=\"fixed-case\">MMP<\/jats:styled-content>\u20109 in different tumor types. However, the underlying mechanism of anti\u2010invasive activity in <jats:styled-content style=\"fixed-case\">HCC<\/jats:styled-content> models has not been fully elucidated. Here, we demonstrate that 1\u00a0m<jats:sc>m<\/jats:sc> melatonin dosage reduced in <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101\u03b2\u2010induced <jats:styled-content style=\"fixed-case\">H<\/jats:styled-content>ep<jats:styled-content style=\"fixed-case\">G<\/jats:styled-content>2 cells <jats:styled-content style=\"fixed-case\">MMP<\/jats:styled-content>\u20109 gelatinase activity and inhibited cell invasion and motility through downregulation of <jats:styled-content style=\"fixed-case\">MMP<\/jats:styled-content>\u20109 gene expression and upregulation of the <jats:styled-content style=\"fixed-case\">MMP<\/jats:styled-content>\u20109\u2010specific inhibitor tissue inhibitor of metalloproteinases (<jats:styled-content style=\"fixed-case\">TIMP<\/jats:styled-content>)\u20101. No significant changes were observed in the expression and activity of <jats:styled-content style=\"fixed-case\">MMP<\/jats:styled-content>\u20102, the other proteinase implicated in matrix collagen degradation, and its tissue inhibitor, <jats:styled-content style=\"fixed-case\">TIMP<\/jats:styled-content>\u20102. Also, melatonin significantly suppressed <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101\u03b2\u2010induced nuclear factor\u2010kappa<jats:styled-content style=\"fixed-case\">B<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010\u03baB) translocation and transcriptional activity. In summary, we demonstrate that melatonin modulates motility and invasiveness of <jats:styled-content style=\"fixed-case\">H<\/jats:styled-content>ep<jats:styled-content style=\"fixed-case\">G<\/jats:styled-content>2 cell in vitro through a molecular mechanism that involves <jats:styled-content style=\"fixed-case\">TIMP<\/jats:styled-content>\u20101 upregulation and attenuation of <jats:styled-content style=\"fixed-case\">MMP<\/jats:styled-content>\u20109 expression and activity via <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010\u03baB signal pathway inhibition.<\/jats:p>","DOI":"10.1111\/jpi.12092","type":"journal-article","created":{"date-parts":[[2013,9,4]],"date-time":"2013-09-04T07:31:33Z","timestamp":1378279893000},"page":"20-30","source":"Crossref","is-referenced-by-count":89,"title":["Inhibition of matrix metalloproteinase\u20109 and nuclear factor kappa <scp>B<\/scp> contribute to melatonin prevention of motility and invasiveness in 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