| Title: |
Taohong Siwu decoction enhances the chemotherapeutic efficacy of doxorubicin by promoting tumor vascular normalization |
| Authors: |
Cheng, Yanfen; Li, Jingjing; Feng, Xi; Wu, Yihan; Wu, Xiaoping; Lau, Benson Wui Man; Ng, Shamay Sheung Mei; Lee, Simon Ming Yuen; Seto, Sai Wang; Leung, George Pak Heng; Hu, Yichen; Fu, Chaomei; Zhang, Siyuan; Zhang, Jinming |
| Publisher Information: |
Elsevier |
| Publication Year: |
2024 |
| Collection: |
University of Hong Kong: HKU Scholars Hub |
| Subject Terms: |
Angiogenesis; Breast cancer; Doxorubicin; Taohong Siwu decoction; Vascular normalization |
| Description: |
Background: Instead of completely suppressing blood vessels inside tumors, vascular normalization therapy is proposed to normalize and prune the abnormal vasculature in tumor microenvironment (TME) to acquire a normal and stable blood flow and perfusion. The theoretical basis for the use of “blood-activating and stasis-resolving” formulas in Traditional Chinese Medicine to treat cancer is highly consistent with the principle of vascular normalization therapy, suggesting the potential application of these traditional formulas in vascular normalization therapy. Purpose: To study the underlying mechanisms of a classical “blood-activating and stasis-resolving” formula, Taohong Siwu decoction (TSD), in enhancing the efficacy of chemotherapy for breast cancer treatment. Study design: HUVECs and transgenic zebrafish embryos were used as the major model in vitro. A 4T1 mouse breast cancer model was applied to study tumor vasculature normalization of TSD and the combination effects with DOX. Results: Our data showed that TSD exhibited anti-angiogenic potential in HUVECs and transgenic zebrafish embryos. After 20 days treatment, TSD significantly normalized the tumor vasculature by remodeling vessel structure, reducing intratumoral hypoxia and vessel leakage, and promoting vessel maturation and blood perfusion in 4T1 breast tumor-bearing mice. Moreover, the anti-tumor efficacy of doxorubicin liposome in 4T1 breast tumors was significantly improved by TSD, including the suppression of tumor cell proliferation, angiogenesis, hypoxia, and the increase of cell apoptosis, which is likely through the vascular normalization induced by TSD. TSD also shifted the macrophage polarization from M2 to M1 phenotype in TME during the combination therapy, as evidenced by the reduced number of CD206+ macrophages and increased number of CD86+ macrophages. Additionally, TSD treatment protected against doxorubicin-induced cardiotoxicity in animals, as evidenced by the reduced cardiomyocytes apoptosis and improved heart function. Conclusion: ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
Phytomedicine; Phytomedicine, 2024, v. 134; WOS:001316661700001; https://hub.hku.hk/handle/10722/353835; 134 |
| DOI: |
10.1016/j.phymed.2024.155995 |
| Availability: |
https://hub.hku.hk/handle/10722/353835; https://doi.org/10.1016/j.phymed.2024.155995 |
| Rights: |
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. |
| Accession Number: |
edsbas.877769AF |
| Database: |
BASE |