Effects of <a name="OLE_LINK12">simvastatin</a> on human breast cancer osteolytic bone metastasis in a nude mice model

Abstract

Abstract:ObjectiveTo observe the effect of simvastatin on bone metastasis of breast cancer in nude mice model. MethodsSixty mice were divided into three groups randomly with 20 in each group. Mice were inoculated with MDAMB231 cells into the left cardiac ventricle. After 7 days, mice were treated with either simvastatin, saline, or nothing twice per week for 19 days. The area of osteolytic metastases was subsequently measured in long bones of all mice using an image analysis system. After sacrifice, parathyroid hormonerelated protein (PTHrP) concentrations in bone marrow from all mice were determined using a twosite immunoradiometric assay. Osteoclast number expressed per millimeter of tumor/bone interface was assessed using an OsteoMeasure System. Measured data were compared with analysis of variance, and P＜0.05 for the difference was statistically significant. ResultsThe area of osteolytic lesions was significantly lower in mice treated with simvastatin compared with mice receiving saline and no treatment (0.51±0.18 mm2 vs 2.13±1.24 mm2 vs 2.29±1.22 mm2; F=15.600, P=0.002; F=15.673, P=0.001). In addition, treatment with simvastatin decreased the concentrations of PTHrP in bone marrow plasma (0.98±0.20 pmol/L vs 2.11±0.31 pmol/L vs 1.99±0.29 pmol/L; F=61.469, P＜0.001; F=58.274, P＜0.001) and the osteoclast numbers per millimeter of tumor/bone interface (4.00±1.73 vs 11.40±4.93 vs 10.91±3.87; F=17.820, P=0.001; F=17.184, P=0.002) compared with controls. ConclusionSimvastatin may reduce the production of PTHrP of breast cancer cells, which suppresses the development of destructive bone lesions as well as the growth of breast cancer cells in bone.

Key words:Breast neoplasms,Neoplasm metastasis,Simvastatin,Parathyroid hormone

Chen Mingxia, Zhang Wei, Qu Jianli, Li Qiang, Wang Hai. Effects ofsimvastatinon human breast cancer osteolytic bone metastasis in a nude mice model[J]. Journal of International Oncology, 2015, 42(1): 5-9.

References

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Effects ofsimvastatinon human breast cancer osteolytic bone metastasis in a nude mice model

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