Acta Pharmacologica Sinica (2009) 30: 1162-1168; doi: 10.1038/aps.2009.94; published online 6 July 2009

Aim: Silibinin is known to exert growth inhibition and cell death together with cell cycle arrest and apoptosis in human prostate cancer cells.  Whether silibinin could inhibit the invasion, motility and migration of prostate cancer cells remains largely unknown.  This study was designed to evaluate this efficacy and possible mechanisms using a novel highly bone metastatic ARCaP_M cell model.

Methods: Four prostate cancer cell lines, LNCaP, PC-3, DU145, and ARCaP_M, were used in this study.  These cells were treated with increasing concentrations of silibinin (50, 100, and 200 μmol/L) for different periods of time.  After treatment, cell viabilities of four prostate cancer cells were compared by MTT assay.  Alterations of ARCaP_M cell invasion, motility and migration were assessed by cell invasion, motility and wound healing assays.  The changes of vimentin expression were observed by Western blotting and immunofluorescence staining, and the expression of MMP-2, MMP-9, and uPA was analyzed by reverse transcription-polymerase chain reaction (RT-PCR).

Results: ARCaP_M cells showed less sensitivity to the growth inhibition of pharmacological doses of silibinin than LNCaP, PC-3, and DU145 cells.  However, silibinin exerted significant dose- and time-dependent inhibitory effects on the invasion, motility and migration of ARCaP_M cells.  Furthermore, the expression of vimentin and MMP-2, but not MMP-9 or uPA, was down-regulated in a dose- and time-dependent manner after treatment of silibinin.

Conclusion: This study shows that silibinin could inhibit the invasion, motility and migration of ARCaP_M cells via down-regulation of vimentin and MMP-2 and therefore may be a promising agent against prostate cancer bone metastasis.

Keywords: silibinin; prostate cancer; invasion; motility; migration; vimentin; MMP-2