Glucocorticoid receptor-induced down-regulation of MMP-9 by ginseng components, PD and PT contributes to inhibition of the invasive capacity of HT1080 human fibrosarcoma cells

We examined the effects of the purified ginseng components, panaxadiol (PD) and panaxatriol (PT), on the expression of matrix metalloproteinase-9 (MMP -9) in highly metastatic HT1080 human fibrosarcoma cell line. A significant down-regulation of MMP-9 by PD and PT was detected by Northern blot analys is. However, the expression of MMP-2 was not changed by treatment with PD a nd PT. Quantitative gelatin based zymography confirmed a markedly reduced e xpression of MMP-9, but not MMP-2 in the treatment of PD and PT, To investi gate whether the reduced level of MMP-9 by PD and PT affects the invasive c apacity of HT1080 cells, we conducted an ill vitro invasion assay with PD a nd PT treated cells. The results of the in vitro invasion assay revealed th at PD and PT reduced tumor cell invasion through a reconstituted basement m embrane in the transwell chamber. Because of the similarity of chemical str ucture between PD, PT and dexamethasone (Dexa), a synthetic glucocorticoid, we investigated whether the down-regulation of MMP-9 by PD and PT were med iated by the nuclear translocation of glucocorticoid receptor (GR), Increas ed GR in the nucleus of HT1080 human fibrosarcoma cells treated by PD and P T was detected by immunocytochemistry, Western blot and gel retardation ass ays confirmed the increase of GR in the nucleus after treatment with PD and PT. These results suggest that GR-induced down-regulation of MMP-9 by PD a nd PT contributes to reduce the invasive capacity of HT1080 cells.