Silibinin inhibits prostate cancer invasion, motility and migration by suppressing vimentin and MMP-2 expression.
OBJECTIVE
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 micromol/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.


CONCLUSIONS
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.
Wu
Kai-jie
KJ
Department of Urology, First Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an 710061, China.
Zeng
Jin
J
Zhu
Guo-dong
GD
Zhang
Lin-lin
LL
Zhang
Dong
D
Li
Lei
L
Fan
Jin-hai
JH
Wang
Xin-yang
XY
He
Da-lin
DL
D000975:Antioxidants / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000517:prevention & control*; D011471:Prostatic Neoplasms / Q000473:pathology*; D000077385:Silybin; D012838:Silymarin / Q000627:therapeutic use; D014746:Vimentin / Q000235:genetics* / Q000378:metabolism
D000975:Antioxidants; D012838:Silymarin; D014746:Vimentin; D000077385:Silybin; D020778:Matrix Metalloproteinase 2