Chinese herbal medicine Baoyuan Jiedu decoction inhibits the accumulation of myeloid derived suppressor cells in pre-metastatic niche of lung via TGF-β/CCL9 pathway

Biomed Pharmacother. 2020 Sep:129:110380. doi: 10.1016/j.biopha.2020.110380. Epub 2020 Jun 15.

Abstract

Baoyuan Jiedu (BYJD for short) decoction, a traditional Chinese medicine formula, is composed of Astragalus, Ginseng, Aconite root, Honeysuckle, Angelica, Licorice, which has the functions of nourishing qi and blood, enhancing immune function, improving quality of life and prolonging survival time of tumor patients. The present study aimed to investigate the effect and mechanism of BYJD decoction on reversing the pre-metastatic niche. We showed that BYJD decoction could prolong the survival time of 4T1 tumor-bearing mice. Moreover, we found that the BYJD decoction inhibited the formation of lung pre-metastatic niche and inhibited recruitment of myeloid derived suppressor cells (MDSCs) in the lung. Mechanistically, we showed that the proteins and genes expression of TGF-β, Smad2, Smad3, p-Smad2/3, Smad4, CCL9 in the TGF-β/CCL9 signaling pathway were suppressed by BYJD decoction. In line with the above findings, our results confirm that BYJD decoction inhibits the accumulation of MDSC in pre-metastatic niche of lung via TGF-β/CCL9 pathway.

Keywords: Myeloid derived suppressor cells; Pre-metastatic niche; TGF-β/CCL9 signaling pathway; Traditional Chinese Medicine.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Chemokines, CC / genetics
  • Chemokines, CC / metabolism*
  • Drugs, Chinese Herbal / pharmacology*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Lung / drug effects*
  • Lung / metabolism
  • Lung / pathology
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / prevention & control*
  • Lung Neoplasms / secondary
  • Macrophage Inflammatory Proteins / genetics
  • Macrophage Inflammatory Proteins / metabolism*
  • Mice, Inbred BALB C
  • Myeloid-Derived Suppressor Cells / drug effects*
  • Myeloid-Derived Suppressor Cells / metabolism
  • Myeloid-Derived Suppressor Cells / pathology
  • Signal Transduction
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism*
  • Tumor Burden / drug effects
  • Tumor Microenvironment*

Substances

  • Antineoplastic Agents, Phytogenic
  • Baoyuan decoction
  • Ccl9 protein, mouse
  • Chemokines, CC
  • Drugs, Chinese Herbal
  • Macrophage Inflammatory Proteins
  • Transforming Growth Factor beta