Effects of simvastatin on human breast cancer osteolytic bone metastasis in a nude mice model
10.3760/cma.j.issn.1673-422X.2015.01.002
- VernacularTitle:辛伐他汀在裸鼠模型中对乳腺癌骨转移的影响
- Author:
Mingxia CHEN
;
Wei ZHANG
;
Jianli QU
;
Qiang LI
;
Hai WANG
- Publication Type:Journal Article
- Keywords:
Breast neoplasms;
Neoplasm metastasis;
Simvastatin;
Parathyroid hormone
- From:
Journal of International Oncology
2015;42(1):5-9
- CountryChina
- Language:Chinese
-
Abstract:
Objective To observe the effect of simvastatin on bone metastasis of breast cancer in nude mice model.Methods Sixty 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.Results The 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.Conclusion Simvastatin 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.
