Anti-Breast Cancer Effects of Vitamin D3 Analogs Either Alone or in Combination with Other Agents

摘要

We have studied the effects of various vitamin D analogs alone and in combination against breast cancer cells. We have found the vitamin D analog EBlO89 to be particularly potent against in vivo breast cancer cells (MCF-7), without causing hypercalcemia or other major side-effects. An additive effect was observed when a vitamin D analog and Taxol were administered together. EBl089 plus Taxol was the most active combination. Our studies have also demonstrated that a peroxisome proliferation activated receptor gamma (PPARgamma) ligand (Troglitazone) has chemopreventive properties in breast cancer. The addition of a RXR-selective ligand appears to enhance this activity. Cyr6l is a gene that has been identified in other tissue types and is associated with angiogenesis and metastasis. We have identified prominent expression of the Cyr6l gene in selected breast cancer cell lines as well as in fresh breast tumors. When we exposed normal breast cells to estrogen and an anti-estrogen, we altered expression of this gene.