Background: Overexpression of MDA-9/Syntenin occurs in multiple human
cancer cell lines and is associated with higher grade of tumor classification,
invasiveness and metastasis. In some cases, its role in cancer biology depends on
relationships between MDA-9/Syntenin and NF-κB.
Objective: This study aims to analyze the presence of a regulation loop like that
between 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 Matrigel
Invasion 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 of
human liver carcinoma (HA22T/VGH, Hep3B and HepG2). In all cell lines there was an
inverse relationship between MDA-9/Syntenin and RKIP expression levels, and a
positive correlation between MDA-9/Syntenin expression and NF-κB activation levels. By
silencing with a siRNA anti-MDA-9/Syntenin we observed in all cell lines a very strong
increase of RKIP at mRNA level. Interestingly, in all cell lines, inhibition of MDA-
9/Syntenin expression induced NF-κB downregulation and contemporary a reduction in
invasion ability MMP-2 dependent. Finally, we showed a good additive effect of MDA-
9/Syntenin siRNA when associated with Curcumin or Doxorubicin on cell growth
Conclusion: Our data confirm the key role of MDA-9/Syntenin in HCC biology. The
presence of a regulation loop among MDA-9/Syntenin, NF-κB and RKIP provide new