Original Article

Wenshen Zhuanggu formula effectively suppresses breast cancer bone metastases in a mouse xenograft model

Authors: Jia-jia LI, Wei-ling CHEN, Jian-yi WANG, Qian-wen HU, Zhen-ping SUN, Shuai ZHANG, Sheng LIU, Xiang-hui HAN

Abstract

Wenshen Zhuanggu formula (WSZG) is a traditional Chinese medicine used as an adjuvant for the prevention of bone metastases in breast cancer patients. In this study we investigated the efficacy of WSZG in preventing bone metastases and the potential mechanisms in a mouse xenograft model of breast cancer bone metastases. This model was established by injection of human MDAMB- 231BO-Luc breast cancer cells alone or a mixture of the cancer cells with bone marrow-derived mesenchymal stem cells (BMSCs) into left ventricle of the heart in female nude mice. Then the mice were treated with WSZG (3.25, 6.5 or 13.0 mg·kg-1·d-1, ig) for four weeks, whereas zoledronic acid (100 μg/kg per week, ig) was used as a positive control. The occurrence and development of bone metastases were monitored via bioluminescent imaging, and bone lesions were assessed using micro-CT. Intracardiac injection of the mixture of MDA-MB-231BO-Luc breast cancer cells with BMSCs significantly facilitated the bone metastatic capacity of the breast cancer cells, and aggravated bone lesions in the mouse xenograft model of breast cancer bone metastases. Administration of WSZG dose-dependently inhibited the incidence and intensity of bone metastases and protected against bone lesions by suppressing osteoclast formation and tumor cell infiltration. Furthermore, administration of WSZG caused a marked reduction in the expression of CCL5/CCR5 and IL-17B/IL-17BR in bone metastatic tissues. The results demonstrate that WSZG exerts potential therapeutic effects in a mouse xenograft model of breast cancer bone metastases, which are partially mediated by weakening the interaction between BMSCs and breast cancer cells in the tumor microenvironment.