Secreted Phosphoprotein 24 kD Inhibits Growth of Human Prostate Cancer Cells Stimulated by BMP-2.

BACKGROUND/AIM Secreted phosphoprotein 24 kD (spp24) has been shown to inhibit bone morphogenetic protein 2 (BMP2)-induced cancer growth in several tumor models. In this study, we aimed to investigate the effects spp24 on the growth of prostate cancer caused by BMP2 in vitro and in vivo. MATERIALS AND METHODS The effects of BMP2 and spp24 on PC-3 cell viability were analyzed using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay. A subcutaneous tumor model and intratibial tumor model was established using PC-3 cells. Tumor growth was assessed through gross examination and radiography during the experiment. Then, after sacrifice, tumor cell apoptosis and tumor cell proliferation were assessed by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay and immunochemical analysis. RESULTS BMP2 stimulated the PC-3 cell proliferation in vitro and spp24 could abolish the effect of BMP2. In a xeneograft tumor model, BMP2 promoted the subcutaneous and intratibial tumor growth, while spp24 dramatically inhibited the tumor growth induced by BMP2. Histological examination showed that spp24 also abolished the BMP2-induced proliferating cell nuclear antigen (PCNA) expression and promoted tumor cell apoptosis. CONCLUSION Spp24 can inhibit the growth of prostate cancer and its bone metastasis induced by BMP2; spp24 may have great potential to be a therapeutic agent in clinical situations.