Establishment of a Model to Evaluate Inhibition of Bone Resorption Induced by Human Prostate Cancer Cells in Nude Mice

Abstract

A model system of human prostate carcinoma in nude mice for searching out a method to protect the bone from cancer cells is described, in which the transplanted human prostate cancer cells were inoculated subcutaneously over the calvaria in nude mice after the periosteum was disrupted. The tumor induced osteolysis associated with osteoclast proliferation accompanied with reactive new bone formation. This osteolysis was evaluated by measuring the increased area of bone resorption by its reduced opacity to X-ray, and histology. Etidronate disodium, a diphosphonate derivative, at a dose of three mg .cntdot./kg .cntdot. and 10 mg .cntdot./kg .cntdot. s.c. protected the bone by decreasing the extent of osteolysis as judged by the above criteria. This inhibition was obtained with no apparent effect on the growth of the tumor. These results are discussed in light of recent clinical work, showing that this animal model is a useful tool to test the effect of new drugs against osteolysis of cancer as well as to study the biology of local interaction between bone and cancer cell.