Additive antitumor activities of taxoids in combination with the bisphosphonate ibandronate against invasion and adhesion of human breast carcinoma cells to bone

A very common metastatic site for breast carcinoma is bone. Metastatic breast carcinoma cells stimulate osteoclast-mediated bone resorption leading to osteolysis. Bisphosphonates are powerful inhibitors of osteoclast activity, and are therefore used in combination with standard chemotherapy or hormonal therapy for the treatment of cancer-associated osteolytic metastases. However, there may be an added beneficial effect of the bisphosphonates, that is, additive or synergistic activities with cytotoxic agents. Here, we investigated the effects of the bisphosphonate ibandronate in combination with taxoids (taxol and taxotere) on induction of apoptosis, invasion and adhesion of breast carcinoma cells to bone. Ibandronate did not induce apoptosis of human MDA-MB-231 breast carcinoma cells, nor did it enhance the effectiveness of taxoid-induced apoptosis in MDA-MB-231 cells. In contrast, ibandronate enhanced the antitumor activity of taxoids against invasion and cell adhesion to bone. Our findings raise the interesting possibility that the combination of bisphosphonates and taxoids may be useful for the treatment of patients with cancer types that are known to metastasize preferentially to bone. Int. J. Cancer 83:263–269, 1999. © 1999 Wiley-Liss, Inc.