Potential Therapeutic Applications of MDA-9/Syntenin-NF-κB-RKIP Loop in Human Liver Carcinoma

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Abstract

Background: Overexpression of MDA-9/Syntenin occurs in multiple humancancer cell lines and is associated with higher grade of tumor classification,invasiveness and metastasis. In some cases, its role in cancer biology depends onrelationships between MDA-9/Syntenin and NF-κB.Objective: This study aims to analyze the presence of a regulation loop like thatbetween MDA-9/Syntenin - NF-κB - RKIP in human liver carcinoma.Methods: Transient transfection was performed with siRNA anti-MDA-9/Syntenin.Expression of different factors was evaluated by Real time-PCR and Western blotting,while NF-κB activation by TransAM assay. Invasion capacity was analyzed by MatrigelInvasion Assay and the effects of agents on cell viability were examined by MTS assay.Results: We have examined basal expression of MDA-9/Syntenin in three cell lines ofhuman liver carcinoma (HA22T/VGH, Hep3B and HepG2). In all cell lines there was aninverse relationship between MDA-9/Syntenin and RKIP expression levels, and apositive correlation between MDA-9/Syntenin expression and NF-κB activation levels. Bysilencing with a siRNA anti-MDA-9/Syntenin we observed in all cell lines a very strongincrease of RKIP at mRNA level. Interestingly, in all cell lines, inhibition of MDA-9/Syntenin expression induced NF-κB downregulation and contemporary a reduction ininvasion ability MMP-2 dependent. Finally, we showed a good additive effect of MDA-9/Syntenin siRNA when associated with Curcumin or Doxorubicin on cell growthinhibition.Conclusion: Our data confirm the key role of MDA-9/Syntenin in HCC biology. Thepresence of a regulation loop among MDA-9/Syntenin, NF-κB and RKIP provide newpharmacological approaches.
Original languageEnglish
Pages (from-to)630-639
Number of pages10
JournalCurrent Molecular Medicine
Volume18
Publication statusPublished - 2018

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology

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