Bushen Huoxue Decoction Reduces Osteoclastogenesis By Downregulating The Expression Of BSP, Src, PTHrP, And NFATc1 In The Treatment Of Breast Cancer Bone Metastasi

Objective: Currently,bone is the most frequent location of breast cancer metastasis,and breast cancer is the malignant tumor with the highest incidence and fatality in women.Patients’ quality of life is significantly impacted by bone metastases,which even puts their lives in danger.Traditional Chinese medicines,many of which have anti-tumor activity and may be useful in treating bone metastases of breast cancer,such as Bushen Huoxue Decoction,are frequently used to treat a number of bone-related disorders.The goal of this study was to determine the influence of Bushen Huoxue decoction on bone metastasis of breast cancer and gene expression levels of BSP,PTHr P,NFATc1,and Src in nude mice.This was done by creating a bone metastasis model of breast cancer in nude mice.Methods: Balb/c6-8 week-old nude mice were labeled according to body weight(n=30).The nude mice were randomly divided into five groups by random number table method: blank control group,model group,traditional Chinese medicine group,zoledronic acid group,and traditional Chinese medicine combined with zoledronic acid group,with 6 mice in each group.The blank control group was injected into the tibia with PBS,and the other four groups were injected into the tibia with 4T1-luc cell suspension to construct bone metastases of breast cancer.After 5 days of modeling,the nude mice were given drug intervention,and the appearance,weight and behavior changes were recorded.After 14 days of continuous administration,the nude mice were sacrificed by taking blood from orbit.Body mass,right hind limb mass detection,tumor tissue HE staining,immunohistochemical detection,tibia X-ray examination,tibia tissue TRAP staining and protein expression of BSP,PTHr P,NFATc1 and Src were analyzed statistically.Results: Compared with nude mice of breast cancer bone metastasis model group,Bushen Huoxue decoction can increase body weight,reduce tumor load and the number of osteoclasts in tibia,down-regulate gene expression levels of BSP,PTHr P,NFATc1 and Src,and effectively improve the degree of bone damage of bone metastasis.When Bushen Huoxue decoction combined with zoledronic acid,the improvement of the above indexes was better than that of Bushen Huoxue decoction or zoledronic acid alone.Conclusion: Bushen Huoxue Decoction has good antitumor activity,which can inhibit osteoclast generation by down-regulating the expressions of BSP,PTHr P,NFATc1 and Src genes,and play a role in the treatment of breast cancer bone metastasis.