Astragalus Polysaccharide RAP Induces Macrophage Phenotype Polarization to M1 via the Notch Signaling Pathway

Macrophages occur in polarized phenotypes, whose characteristics determine the role they play in tumor growth. The M1 phenotype macrophages promote tumoricidal responses and suppress tumor growth. Our previous study showed that a polysaccharide isolated from Radix Astragali, named RAP, was itself no...

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Bibliographic Details
Published in:Molecules (Basel, Switzerland) Switzerland), 2019-05, Vol.24 (10), p.2016
Main Authors: Wei, Wei, Li, Zhi-Peng, Bian, Zhao-Xiang, Han, Quan-Bin
Format: Article
Language:English
Subjects:
Animals
Astragali Radix
Astragalus membranaceus
Astragalus Plant - chemistry
Biomarkers - metabolism
Bone marrow
Cell Line, Tumor
Cell Polarity - drug effects
Cell Shape - drug effects
CXCL10 protein
Cytotoxicity
Gene expression
Gene Expression Regulation - drug effects
Genotype & phenotype
Interleukin 6
M1 markers
Macrophages
Macrophages - cytology
Macrophages - drug effects
Macrophages - metabolism
Medical prognosis
Mice
Mice, Inbred BALB C
Morphology
Nitric-oxide synthase
Notch signaling
Phenotype
Phenotypes
Polarization
polysacchairdes
Polysaccharides
Polysaccharides - pharmacology
RAW 264.7 Cells
Receptors, Notch - metabolism
Secretase
Signal Transduction
Tumor Burden - drug effects
Tumor cells
Tumor necrosis factor-α
tumoricidal responses
Tumors
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Summary:Macrophages occur in polarized phenotypes, whose characteristics determine the role they play in tumor growth. The M1 phenotype macrophages promote tumoricidal responses and suppress tumor growth. Our previous study showed that a polysaccharide isolated from Radix Astragali, named RAP, was itself non-cytotoxic but induced RAW264.7 cells' cytotoxicity against cancer cells. The current study was undertaken to determine its mechanism. Series studies was conducted to show that RAP is able to induce much higher gene expression of M1 markers, including iNOS, IL-6, TNF-a, and CXCL10, compared with the control group. When RAP-induced BMDMs were transplanted together with 4T1 tumor cells in BALB/c mice, both tumor volume and tumor weight decreased. Further studies indicated that RAP induces the Notch signaling pathway in RAW264.7 cells. The function of Notch signaling in macrophage polarization was confirmed by using γ-secretase inhibitor. These results suggested that polysaccharide RAP induces macrophage's polarization to M1 phenotype via the Notch signaling pathway.
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules24102016