Identification of bioactive anti-angiogenic components targeting tumor endothelial cells in Shenmai injection using multidimensional pharmacokinetics
| Autor: | Qixiang Zhang, Qi-zhi Wang, Xuequan Yao, Pei-Qiang Shen, Jingwei Zhang, Huan Wang, Wenyue Liu, Suiying Ni, Jiali Liu, Chao Jiang, Guangji Wang, Chongjin Zhong, Fang Zhou, Wang Mulan, Min Jin, Lingge Cheng |
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| Rok vydání: | 2020 |
| Předmět: |
Tumor endothelial cell
Colorectal cancer Anti-angiogenic medicine.medical_treatment education Multidimensional pharmacokinetics Neovascularization 03 medical and health sciences 0302 clinical medicine Pharmacokinetics Ginsenoside Rd Adjuvant therapy medicine General Pharmacology Toxicology and Pharmaceutics 030304 developmental biology Tube formation 0303 health sciences Chemotherapy Shenmai injection Chemistry lcsh:RM1-950 Anti angiogenic Cancer medicine.disease lcsh:Therapeutics. Pharmacology 030220 oncology & carcinogenesis Cancer research Original Article medicine.symptom |
| Zdroj: | Acta Pharmaceutica Sinica. B Acta Pharmaceutica Sinica B, Vol 10, Iss 9, Pp 1694-1708 (2020) |
| ISSN: | 2211-3835 |
| DOI: | 10.1016/j.apsb.2019.12.011 |
| Popis: | Shenmai injection (SMI) is a well-defined herbal preparation that is widely and clinically used as an adjuvant therapy for cancer. Previously, we found that SMI synergistically enhanced the activity of chemotherapy on colorectal cancer by promoting the distribution of drugs in xenograft tumors. However, the underlying mechanisms and bioactive constituents remained unknown. In the present work, the regulatory effects of SMI on tumor vasculature were determined, and the potential anti-angiogenic components targeting tumor endothelial cells (TECs) were identified. Multidimensional pharmacokinetic profiles of ginsenosides in plasma, subcutaneous tumors, and TECs were investigated. The results showed that the concentrations of protopanaxadiol-type (PPD) ginsenosides (Rb1, Rb2/Rb3, Rc, and Rd) in both plasma and tumors, were higher than those of protopanaxatriol-type (Rg1 and Re) and oleanane-type (Ro) ginsenosides. Among PPD-type ginsenosides, Rd exhibited the greatest concentrations in tumors and TECs after repeated injection. In vivo bioactivity results showed that Rd suppressed neovascularization in tumors, normalized the structure of tumor vessels, and improved the anti-tumor effect of 5-fluorouracil (5FU) in xenograft mice. Furthermore, Rd inhibited the migration and tube formation capacity of endothelial cells in vitro. In conclusion, Rd may be an important active form to exert the anti-angiogenic effect on tumor after SMI treatment. Graphical abstract Shenmai injection (SMI) enhanced the anti-tumor effect of 5FU and normalized tumor vessels. Pharmacokinetic (PK) differences among the various components in SMI resulted in Rd being the most abundant component in tumor endothelial cells (TECs). This study proves that Rd may be an important active form to normalize tumor vessels.Image 1 |
| Databáze: | OpenAIRE |
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