Jianpi Yangzheng Xiaozheng Prescription inhibiting lung pre-metastatic niche formation of gastric cancer through reducing gastric cancer exosome PD-L1
10.3760/cma.j.cn115398-20240708-00089
- VernacularTitle:健脾养正消癥方减少胃癌外泌体PD-L1抑制胃癌肺转移前微环境形成
- Author:
Cancan ZHANG
1
;
Yanzhen CHEN
;
Xingxing ZHANG
;
Wenjie LI
;
Bo HAN
;
Yaqi LI
;
Jian WU
;
Shenlin LIU
Author Information
1. 南京中医药大学附属医院2022级硕士研究生，南京 210023
- Keywords:
Stomach neoplasms;
Exosomes;
programmed death receptor ligand 1;
Myeloid-derived suppressor cells;
Tumor-associated macrophages;
Pre-transfer microenvironm
- From:
International Journal of Traditional Chinese Medicine
2025;47(6):798-806
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effects and mechanism of Jianpi Yangzheng Xiaozheng Prescription in lung pre-metastatic niche formation of gastric cancer by regulating the content of programmed death receptor ligand 1 (PD-L1) in gastric cancer exosomes.Methods:Totally 30 615 mice were divided into normal group, model group, Jianpi Yangzheng Xiaozheng Prescription low- and high-dosage groups, and exosome inhibitor group according to random number table method, with 6 mice in each group. The mouse model of lung pre-metastatic niche formation of gastric cancer was established by tail vein injection of MFC cells. After 12 days of administration, the lung metastasis under the intervention of Jianpi Yangzheng Xiaozheng Prescription was evaluated by observing the infiltration of tumor into lung tissue, weighing lung weight and hematoxylin-eosin (HE) staining of lung tissue. Mouse serum exosomes were extracted by ExoQuick kit and identified by transmission electron microscopy and nanoparticle tracking analysis (NTA). The content of PD-L1 in serum exosomes and the expression levels of serum transforming growth factor-β (TGF-β), interleukin-10 (IL-10) and interleukin-6 (IL-6) were detected by enzyme-linked immunosorbent assay (ELISA). Immunofluorescence was used to detect the phenotype of myeloid-derived suppressor cells (MDSC) and tumor-associated macrophages (TAM) and the expression of PD-L1 in MDSC and TAM.Results:Compared with the model group, after the intervention of Jianpi Yangzheng Xiaozheng Prescription, the lung metastases of mice were reduced ( P<0.05), and the weight of metastatic tumors decreased ( P<0.05). PD-L1 in serum exosomes and the proportion of MDSC and M2 TAM in lung tissue microenvironment decreased, as well as the expression of PD-L1 on MDSC and TAM decreased ( P<0.05). The serum levels of IL-10 and IL-6 significantly decreased ( P<0.05). Conclusion:Jianpi Yangzheng Xiaozheng Prescription can reduce the proportion of MDSC and M2 TAM and the expression level of PD-L1 in the microenvironment of lung tissue before metastasis by inhibiting the transmission of gastric cancer exosome PD-L1 to MDSC and TAM, and reduce the contents of inflammatory factorsIL-10 and IL-6, so as to play a role in improving the microenvironment before lung metastasis of gastric cancer.
