Polysaccharide is one of main components in Polygonatum sibiricum (PS), which is an herbal medicine widely used in East Asia. Polysaccharides from Polygonatum sibiricum has been shown to exhibit multiple biological activities, such as anti-diabetes, anti-inflammation, antioxidant, immunity modulation, and anticancer. Since hematopoietic system is one of determinant factors in cancer control, we here explored the effect of polysaccharide-rich extract from Polygonatum sibiricum (PREPS) on hematopoiesis in the mice bearing triple negative breast cancer (TNBC). We found that the 4T1 TNBC tumor significantly increased myeloid cells in peripheral blood, bone marrow and spleen, while decreasing bone marrow hematopoietic stem and progenitor cells (HSPCs), indicative of an inhibition of medullary hematopoiesis. When 4T1 TNBC tumor-bearing mice were treated with PREPS, the percentage of myeloid cells within tumor-infiltrating immune cells was reduced. In addition, PREPS also inhibited hematopoietic cell expansion in the spleen, which was induced by TNBC tumors. Importantly, PREPS markedly increased HSPCs and common lymphoid progenitors in the bone marrow that had been suppressed by TNBC tumors. These findings suggest that PREPS protect hematopoiesis inhibited by TNBC tumors in the bone marrow. Although PREPS alone did not achieve statistical significance in the suppression of TNBC tumor growth, it may have a long-lasting anti-tumor effect to assist TNBC therapies by sustaining hematopoiesis and lymphoid regeneration in bone marrow.

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.

Background: The therapy for breast cancer bone metastasis (BCBM) still needs profound investigation. Focusing on the formation of bone pre-metastasis niche (BPMN) is a crucial tache for BCBM treatment. Wenshen Zhuanggu Formula (WSZG) is a typical traditional Chinese medicine (TCM) prescription with ability of clinically palliating bone pain and ameliorating the quality of life of BCBM patients. This study aims to elucidate the inhibitory effect and underlying mechanism of WSZG on BPMN formation induced by tumor-derived exosomes. Methods: Bone precursor cells were exposed to exosomes derived from MDA-MB-231BO cells (BO-exo, 50 μg/mL) and treated by WSZG (10 or 20 μg/mL) in vitro. A primary breast cancer mouse model with propensity of BPMN was established by pre-educating BO-exo and then subcutaneously injecting MDA-MB-231BO cells into mammary fat pads. After the modeled mice were orally administrated WSZG (6.5 or 13 g crude herb kg⁻¹ d⁻¹) for 28 days, bone architecture and bone parameters of tibia were analyzed using micro-CT. The absorbed exosomes by bone precursor cells were investigated using confocal microscopy. Osteoclastic and osteoblastic differentiation were examined by TRAP, ALP and qRT-PCR. The levels of protein related to bone metabolism and extracellular matrix (ECM) were detected by ELISA and IHC methods. Results: The results showed that BO-exo elicited the vicious bone microenvironment to form BPMN in bone-tropic primary BC mice. WSZG encouragingly targeted BO-exo to hinder osteoclastic differentiation (ACP5, c-Fos, Ctsk, MMP9, NFATc1), improve focal bone lesions (BMD, Tb.N, Tb.Th, Tb.Sp, Conn-Dens. and BV/TV), and downregulate the expression levels of bone metabolism markers (ICTP, BALP, TRACP-5b) and bone ECM proteins (bone sialoprotein, elastin, fibronectin, osteopontin, collagen I and vitronectin). Conclusions: This study denotes the enhanced effects of BO-exo and highly inhibitive possibility by WSZG treatment on BPMN formation, shaping bone metastatic landscape of BC and informing the treatment of early-stage BCBM in terms of TCM.