4.6 Article

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

Journal

MOLECULES
Volume 24, Issue 10, Pages -

Publisher

MDPI
DOI: 10.3390/molecules24102016

Keywords

Astragali Radix; tumoricidal responses; M1 markers; Notch signaling; macrophages; polysacchairdes

Funding

  1. HKSAR Innovation and Technology Fund (ITF), Tier 3 [ITS/311/09]
  2. Health Medical Research Fund [11122531, 14150521]
  3. National Natural Sciences Foundation in China [81473341]
  4. Hong Kong Baptist University [FRG2/17-18/060]
  5. General Research Fund [12100615, 22100014]
  6. Hong Kong Baptist University (RC-start up grant)

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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 -secretase inhibitor. These results suggested that Astragalus polysaccharide RAP induces macrophage's polarization to M1 phenotype via the Notch signaling pathway.

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