Wenshen Zhuanggu formula inhibits tumor-exosomes induced bone pre-metastasis niche formation in primary breast cancer mice
Abstract 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) prescripti...
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BMC
2025-06-01
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| Series: | Chinese Medicine |
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| Online Access: | https://doi.org/10.1186/s13020-025-01136-8 |
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| author | Qionglian Huang Hanjuan Ning Jue Wang Weiwei Liu Sheng Liu Jianyi Wang Xianghui Han |
| author_facet | Qionglian Huang Hanjuan Ning Jue Wang Weiwei Liu Sheng Liu Jianyi Wang Xianghui Han |
| author_sort | Qionglian Huang |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-44400f49daf1419c8494f18359ec5dfe |
| institution | OA Journals |
| issn | 1749-8546 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Chinese Medicine |
| spelling | doaj-art-44400f49daf1419c8494f18359ec5dfe2025-08-20T02:37:35ZengBMCChinese Medicine1749-85462025-06-0120111910.1186/s13020-025-01136-8Wenshen Zhuanggu formula inhibits tumor-exosomes induced bone pre-metastasis niche formation in primary breast cancer miceQionglian Huang0Hanjuan Ning1Jue Wang2Weiwei Liu3Sheng Liu4Jianyi Wang5Xianghui Han6Institute of Chinese Traditional Surgery, Longhua Hospital, Shanghai University of Traditional Chinese MedicineInstitute of Chinese Traditional Surgery, Longhua Hospital, Shanghai University of Traditional Chinese MedicineInstitute of Chinese Traditional Surgery, Longhua Hospital, Shanghai University of Traditional Chinese MedicineInstitute of Chinese Traditional Surgery, Longhua Hospital, Shanghai University of Traditional Chinese MedicineInstitute of Chinese Traditional Surgery, Longhua Hospital, Shanghai University of Traditional Chinese MedicineDepartment of Liver Disease, Shanghai Yueyang Integrated Traditional Chinese Medicine and Western Medicine Hospital Affiliated to Shanghai University of Traditional Chinese MedicineInstitute of Chinese Traditional Surgery, Longhua Hospital, Shanghai University of Traditional Chinese MedicineAbstract 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.https://doi.org/10.1186/s13020-025-01136-8Breast cancerBone pre-metastasis nicheExosomeWenshen Zhuanggu formulaBone microenvironment |
| spellingShingle | Qionglian Huang Hanjuan Ning Jue Wang Weiwei Liu Sheng Liu Jianyi Wang Xianghui Han Wenshen Zhuanggu formula inhibits tumor-exosomes induced bone pre-metastasis niche formation in primary breast cancer mice Chinese Medicine Breast cancer Bone pre-metastasis niche Exosome Wenshen Zhuanggu formula Bone microenvironment |
| title | Wenshen Zhuanggu formula inhibits tumor-exosomes induced bone pre-metastasis niche formation in primary breast cancer mice |
| title_full | Wenshen Zhuanggu formula inhibits tumor-exosomes induced bone pre-metastasis niche formation in primary breast cancer mice |
| title_fullStr | Wenshen Zhuanggu formula inhibits tumor-exosomes induced bone pre-metastasis niche formation in primary breast cancer mice |
| title_full_unstemmed | Wenshen Zhuanggu formula inhibits tumor-exosomes induced bone pre-metastasis niche formation in primary breast cancer mice |
| title_short | Wenshen Zhuanggu formula inhibits tumor-exosomes induced bone pre-metastasis niche formation in primary breast cancer mice |
| title_sort | wenshen zhuanggu formula inhibits tumor exosomes induced bone pre metastasis niche formation in primary breast cancer mice |
| topic | Breast cancer Bone pre-metastasis niche Exosome Wenshen Zhuanggu formula Bone microenvironment |
| url | https://doi.org/10.1186/s13020-025-01136-8 |
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