Inhibitory Effects Of Celecoxib In Combination With Minocycline On Growth Of Breast Cancer Bone Metastasis: An Experiment Study

BackgroundBreast cancer bone metastasis which occupy 70% of the distant metastasis is one of the most common clinical disease. It can cause hypercalcemia, focal baryodynia, pathologic fracture and so on. Its mechanism has not been made clear , we now have no effective method to synteresis and therapy. However, as generally acknowledged, the growth and metastasis of tumor have close cooperation with Vascularization and tumor extracellular matrix (ECM). So the method—angiogenesis inhibitor combine with matrix metalloproteinase (MMP) inhibitor—is thought to be a new idea. In this study, we utilized Celecoxib as angiogenesis inhibitor, Minocycline as matrix metalloproteinase inhibitor to therapy breast cancer bone metastasis nude mouse model, and the result were positive. Meanwhile, the effect mechanism of these two drug had also been dicussed. ObjectiveEstablish a breast cancer bone metastasis nude mouse model, and investigate the effect of Celecoxib and Minocycline on breast cancer bone metastasis formation and growth. Methods24 breast cancer bone metastasis nude mice were randomly divided into 4 groups, control group (intraperitoneally injected with physiological saline every second day), the Celecoxib group (Celecoxib 30 mg.kg~-1), the Minocycline group (Minocycline 40 mg .kg~-1), the combined group (Celecoxib mg.kg~-1 + Minocycline mg.kg~-1). The mice were sacrificed 30 days later. Immunohistological and image analysis were performed for MVD, VEGF and MMP-9 determination, flow cytometry for tumor cell apoptosis analysis.Result1.Significant inhibition of tumor growth were seen in all treatment groups with an inhibition rate of 50.47%, 53.73% and 70.09%.2.Compared with the control group, the tumor tissue MVD and MMP-9 of all the treatment group were significantly reduced.3.The apoptosis index and serum alkaline phosphate also increased. Conclusionl.Both Celecoxib and Minocycline can inhibit the growth and neoangiogenesis in this breast cancer bone metastasis nude mouse model. When combined with each other, synergism could be achieved, enhancing the antitumor effect.2.Celecoxib could inhibit angiogenesis, and Minocycline could inhibit degradation of ECM. Both of them could enhance apoptosis.