silibinin inhibits tgf-β-induced mmp-2 and mmp-9 through smad signaling pathway in colorectal cancer ht-29 cells

Background: metastasis of cancer cells is the primary responsible for death in patients with colorectal cancer (crc). transforming growth factor-β (tgf-β)-induced matrix metalloproteinases (mmps) are essential for the metastasis process. silibinin is a natural compound extracted from the silybum marianum that exhibits anti-neoplastic activity in cancer cell lines. in this study, we evaluated the effects of silibinin on mmp-2 and mmp-9 induced by tgf-β in human ht-29 crc cell line and the potential mechanism underlying the effects. methods: the present in vitro study was done on the ht-29 cell line. the ht-29 cell line was cultured in rpmi1640 and exposed to tgf- β (5 ng/ml) in the absence and presence of different concentrations of silibinin (10, 25, 50, and 100 μm). the effect of silibinin on ht-29 cell viability was measured with the mtt assay. a real-time polymerase chain reaction (real-time pcr) determined the relative mrna expression of mmp-2 and mmp-9. western blotting was employed to examine mmp-2 and mmp 9 protein expression and smad2 phosphorylation. results: silibinin inhibits cell viability of ht-29 cell line at 24 hours in a dose-dependent manner. tgf-β increased the mrna and protein expression of mmp-2, mmp-9, and phosphorylated smad2 compared to controls. pharmacological inhibition with silibinin markedly blocked tgf-β–induced mmp-2 and mmp-9 mrna and protein expression and smad2 phosphorylation. conclusion: silibinin decreased the cell viability of ht-29 cancer cells in a dose-dependent manner. silibinin also inhibited tgf-β-stimulated mmp-2 and mmp-9 expression in ht-29 cells, possibly mediated with the smad2 signaling pathway.