WSZG inhibits BMSC-induced EMT and bone metastasis in breast cancer by regulating TGF-β1/Smads signaling

• Published in: Biomedicine & pharmacotherapy Vol. 121; p. 109617
• Main Authors: Ma, Jiao, Li, Jiajia, Wang, Ying, Chen, Weiling, Zheng, Peiyong, Chen, Yueqiang, Sun, Zhenping, Liu, Jin, Zhou, Yin, Wang, Jianyi, Liu, Sheng, Han, Xianghui
• Format: Journal Article
• Language: English
• Published: Elsevier Masson SAS 01.01.2020; Elsevier
• Subjects: Bone; Bone marrow-derived mesenchymal stem cell; Breast cancer; Epithelial-mesenchymal transition; Metastasis; Wenshen Zhuanggu Formula; WSZG; AIOD; IHC; H&E; ZA; Breast cancer; real-time PCR; Metastasis; Bone marrow-derived mesenchymal stem cell; MTT; EMT; BMSC-CM; DMEM; Ct; Epithelial-mesenchymal transition; OD; Wenshen Zhuanggu Formula; TGF-β1; Bone; BMSCs; BLI; TCM; ELISA
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2019.109617

[Display omitted] •BMSCs enhance the invasive and metastatic potentials of breast cancer cells by inducing EMT process.•WSZG exerts the potential anti-proliferative and anti-metastatic activities on different breast cancer cells.•WSZG suppresses BMSC-mediated EMT and bone metastasis in breast cancer by downregulating TGF-β1/Smads signaling. Bone metastasis of breast cancer causes severe skeletal-related events and poor prognosis. Wensheng Zhuanggu Formula (WSZG), a traditional Chinese prescription, is used to adjunctively treat breast cancer bone metastases in clinical practice. This study was undertaken to investigate the antibone-metastatic activities and mechanisms of WSZG extract by evaluating the effect of this formula on the cross-talk between bone marrow-derived mesenchymal stem cells (BMSCs) and breast cancer cells in triggering epithelial-mesenchymal transition (EMT) in vivo and in vitro. The results demonstrated that BMSCs might enhance the invasive and metastatic potentials of breast cancer cells as a consequence of EMT induction through direct cell-to-cell contact. WSZG treatment remarkably suppressed motility, invasion, EMT-related gene, and protein markers in BMSC-conditioned breast cancer cells and ameliorated bone metastases and damages in nude mice following co-injection of BMSCs and MDA-MB-231BO breast cancer cells. Further investigation showed that the transforming growth factor-β1 (TGF-β1)/Smads pathway was an important mechanism enabling BMSCs to induce EMT occurrence of breast cancer cells. WSZG treatment reversed BMSC-induced EMT by downregulating TGF-β1/Smads signaling. Thus, WSZG extracts may be regarded as a potential antibone-metastatic agent for breast cancer therapy.