Inhibition of Breast Cancer-lnduced Bone Pain, Metastasis, and Osteolysis in Nude Mice by LOVAZA and DHA Fatty Acids.

摘要

An estimated 192,370 women in USA will be diagnosed with breast cancer and 40,170 will die in 2009. Further, there were approximately 2,533,193 women in USA living with breast cancer in 2006. Among them, many will develop bone metastasis and will have poor quality of life each year. Metastatic bone disease is a major cause of morbidity in breast cancer patients. It is suspected that the microenvironment of the bone may be influenced by dietary factors and adiposity in the bone marrow may influence bone metastasis and osteolysis. We have observed that corn oil enriched diet increases obesity and also adipocytes in bone marrow while omega-3 fatty acids show reduced adipocytes and inflammation. We therefore carried out studies using omega-3 fatty acids both in vitro and in vivo. Our recent studies on proliferation of MDA-231BO cells demonstrated a dose dependent inhibition of tumor cells in vitro by EPA and DHA, the latter being more pronounced in its activity. Similarly, matrigel invasion of MDA-231BO breast cancer cells showed significant reduction of tumor cell invasion by eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Based on these encouraging observations, we carried out a new study using concentrated EPA (EPA 55% and DHA 5%) and DHA (DHA 60% and EPA 5%) obtained from Ocean Nutrition, Canada. We fed 4 week old nude mice with regular control chow diet, 10% EPA and 10% DHA for 1 month (n=10). Mice in each group were injected with 1x10(exp 5) MDA-231BO breast cancer cells intracardially. After four weeks, all mice were scanned by X-ray to measure bone osteolysis followed by histomorphology of both leg joints to evaluate tumor proliferation. It was noted that mice fed DHA show very minimal proliferation and osteolysis. Also, osteolysis in the tibial metaphysis was significantly lower in DHA fed mice. The tumor cell proliferation in tibial metaphysis was measured and tumor cell proliferation was markedly lower in DHA fed mice.