Bisphosphonates (BPs) have already proven to be useful in the treatment of bone metastasis in prostate cancer (PCa) to affect not only osteoclast but may play have a direct anti-tumor effect. In the present study, the third generation BP, YM529 (minodoronate) was administered intra-peritoneally every week post-transplantation. Compared with non-treated group, both osteolytic and osteoblastic changes were inhibited both radiographically and histologically.demonstrating efficacy of YM529. In vitro, YM529 inhibited both the proliferation and invasion of both cell types in a dose-dependent manner. The SDF-1/CXCR-4 pathway is believed to play an important role in the establishment and progression of bone metastasis lesions as osteoblasts secrete SDF-1 and PCa cells express CXCR-4. We therefore investigated whether BPs may affect the SDF-1/CXCR-4 pathway. YM529 suppressed CXCR-4 expression in PC-3 and LNCaP-SF in a dose-dependent manner in vitro. Moreover, immunohistochemical analysis showed that YM529 also attenuated CXCR-4 expression in PC-3 and LNCaP-SF cells transplanted into tibia. In recent years, relation of various chemokine and its receptor are presented for cancer metastasis. These results suggest BPs may inhibit cancer cell invasion to bone matrix mediating through repression of CXCR-4 expression in bone metastasis lesion.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]