Cancer metastasis, involving multiple processes and various cytophysiological changes, is a primary cause of
cancer death and may complicate the clinical management, even lead to death.
Silibinin is a
flavonoid antioxidant and wildly used for its antihepatotoxic properties and recent studies have revealed pleiotropic anticancer and antiproliferative capabilities of
silibinin. In this study, we first observed that
silibinin exerted a dose- and time-dependent inhibitory effect on the invasion and motility, but hardly on the adhesion, of highly metastatic A549 cells in the absence of cytotoxicity. To look at the precise involvement of
silibinin in
cancer metastasis, A549 cells were treated with
silibinin at various concentrations, up to 100 microM, for a defined period and then subjected to
gelatin zymography,
casein zymography and Western blot to investigate the impacts of
silibinin on metalloproteinase-2 (MMP-2),
urokinase plasminogen activator (
u-PA), and
tissue inhibitor of metalloproteinase-2 (TIMP-2), respectively. The results showed that a
silibinin treatment may decrease the expressions of MMP-2 and
u-PA in a concentration- and time-dependent manner and enhance the expression of
TIMP-2. Further analysis with semi-quantitative RT-PCR showed that
silibinin may regulate the expressions of MMP-2 and
u-PA on the transcriptional level while on the translational or post-translational level for
TIMP-2.