Matrix metalloproteinases (
MMPs) play an important role in
glioma infiltration, facilitating cell migration and
tumor invasion through their ability to degrade the extracellular matrix. Therefore, the inhibition of
MMPs has been suggested to be a promising therapeutic strategy for
brain tumors. This study examined the effect of
ginsenoside Rh2 on the expression of
MMPs in human
astroglioma cells. Rh2 inhibited the PMA-induced
mRNA expression of MMP-1, -3, -9, and -14, suggesting that Rh2 has a broad-spectrum inhibitory effect on
MMPs. The molecular mechanism underlying MMP-9 inhibition was further investigated because MMP-9 plays a major role in the invasiveness of
glioma. It was found that Rh2 inhibited the secretion and
protein expression of MMP-9 induced by PMA in human
astroglioma cells. The Rh2-mediated inhibition of MMP-9 gene expression appears to occur through
NF-kappaB and
AP-1 because their
DNA binding and transcriptional activities were suppressed by the agent. Furthermore, Rh2 significantly repressed the PMA-mediated activation of
p38 MAPK, ERK and JNK, which are upstream modulators of
NF-kappaB and
AP-1. Finally, Rh2 inhibited the in vitro invasiveness of
glioma cells, which might be attributed to the broad-spectrum inhibition of
MMPs by Rh2. Overall, the strong inhibition of
MMP expression by Rh2 might provide a potential therapeutic modality for
brain tumors.