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Inhibitory Effect of Astragalus Polysaccharide on Premetastatic Niche of Lung Cancer through the S1PR1-STAT3
Ming Shen1,2,3,4, Yan-Jun Wang5, Zhao-Hua Liu1,2,3,4
1School of Basic Medicine, Gansu University of Chinese Medicine, Lanzhou, China.
Abstract:
As a common malignant tumor, the morbidity and mortality of lung cancer have been rising in recent years. The concept of "premetastatic niche" may lead to a revolutionary change in antitumor metastasis therapeutic strategies. Traditional Chinese medicine with multitargets and lower poisonous agents may be a potentially effective means to intervene in the "premetastatic niche (PMN)" to prevent and treat tumor metastasis. Astragalus polysaccharide (APS) is a substance with strong immune activity in Astragalus membranaceus that has excellent biological activities such as immunomodulation, anti-inflammatory, and antitumor. In this study, we constructed a tumor lung metastasis animal model to explore the intervention mechanism of APS on the premetastatic niche. We found that APS inhibited the formation of the lung premetastatic niche and inhibited the recruitment of myeloid-derived suppressor cells (MDSCs) in the lung. Mechanistically, we showed that the proteins and gene expression of S1PR1, STAT3, and p-STAT3 in the S1PR1/STAT3 signaling pathway were suppressed by APS. In line with the above findings, our results confirmed that APS may inhibit the accumulation of MDSCs in the premetastatic niche through the intervention of the S1PR1-STAT3 signaling pathway to achieve the antitumor effect.
Insights
Astragalus polysaccharide (APS) combats lung cancer metastasis by targeting the premetastatic niche. It inhibits myeloid-derived suppressor cells (MDSCs) via the S1PR1-STAT3 pathway, offering a novel therapeutic strategy.
Area of Science:
- Oncology
- Immunology
- Pharmacology
Background:
- Lung cancer morbidity and mortality are increasing globally.
- The premetastatic niche (PMN) concept offers new therapeutic targets for metastasis.
- Traditional Chinese medicine, like Astragalus polysaccharide (APS), shows potential in cancer treatment.
Purpose of the Study:
- To investigate the intervention mechanism of APS on the premetastatic niche in lung cancer metastasis.
- To explore APS's effect on myeloid-derived suppressor cells (MDSCs) and the S1PR1/STAT3 signaling pathway.
Main Methods:
- Construction of a tumor lung metastasis animal model.
- Assessment of APS's impact on lung premetastatic niche formation and MDSC recruitment.
- Analysis of S1PR1, STAT3, and p-STAT3 protein and gene expression in the S1PR1/STAT3 signaling pathway.
Main Results:
- APS significantly inhibited the formation of the lung premetastatic niche.
- APS suppressed the recruitment of myeloid-derived suppressor cells (MDSCs) in the lung.
- APS downregulated the expression of S1PR1, STAT3, and p-STAT3 within the S1PR1/STAT3 signaling pathway.
Conclusions:
- Astragalus polysaccharide (APS) demonstrates potential in preventing and treating lung cancer metastasis.
- APS inhibits MDSC accumulation in the premetastatic niche by modulating the S1PR1-STAT3 signaling pathway.
- APS represents a promising therapeutic agent for lung cancer metastasis intervention.
