Gadolinium inhibits prostate cancer PC3 cell migration and suppresses osteoclast differentiation in vitro

This study examined whether Gd (gadolinium) could suppress prostate cancer cell migration and prostate cancer cellinduced osteoclast differentiation. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide] and colony forming assay showed that GdCl ₃ treatment inhibited both cell viability and colony forming ability in PC3 cells more significantly than that in DU145 cells. Annexin/PI (propidium iodide) staining showed an increase in apoptotic death of PC3 cells in the presence of GdCl ₃. Wound healing and adhesion assay indicated that GdCl ₃ suppressed PC3 cell migration. Western-blot analysis demonstrated that GdCl ₃ treatment inhibited phosphorylation of ERK (extracellular-signal-regulated kinase) and p38 MAPK (mitogen-activated protein kinase). Pretreatment with PTx (pertussis toxin), a Gi protein inhibitor, conferred resistance to GdCl ₃-induced colony formation, ERK and p38 phosphorylation in PC3 cells. Moreover, GdCl ₃ inhibited PC3 cell-induced osteoclast differentiation. RT-PCR (reverse transcription-PCR) indicated that GdCl ₃ decreased the expression of RANKL (receptor activator of nuclear factor-κB ligand) in PC3 cells, whereas it increased the expression of OPG (osteoprotegerin) in PC3 and DU145 cells. In conclusion, the present study indicated that GdCl ₃ inhibited PC3 cell migration mediated by the inactivation of both ERK and p38 MAPK pathways via PTx-sensitive G proteins, and also suppressed PC3 cell-induced osteoclast differentiation via regulating the mRNA expression of OPG and RANKL.