Study on the Regulation of Polarization of Tumor-associated Macrophages in Mice with Gastric Cancer by Hewei Xiaoliu For-mula and Its Mechanism
10.16466/j.issn1005-5509.2025.04.002
- VernacularTitle:和胃消瘤方调控胃癌小鼠肿瘤相关巨噬细胞极化及其作用机制研究
- Author:
Mengqi CHENG
1
;
Shuhan WANG
;
Hua DUAN
Author Information
1. 浙江中医药大学附属第一医院(浙江省中医院)杭州 310006;浙江中医药大学中西医结合肿瘤研究所
- Publication Type:Journal Article
- Keywords:
Hewei Xiaoliu Formula;
gastric cancer;
tumor micro-environment;
tumor-associated macrophages;
HGC-27 cell;
polarization;
PROX1;
IFN-γ
- From:
Journal of Zhejiang Chinese Medical University
2025;49(4):401-411
- CountryChina
- Language:Chinese
-
Abstract:
[Objective]To research the efficacy of Hewei Xiaoliu Formula in inhibiting gastric cancer and its effect on the polarization of tumor-associated macrophages(TAM),and to explore its mechanism.[Methods]The mouse model of HGC-27 gastric cancer was established to observe the effect of Hewei Xiaoliu Formula on the tumor weight,volume and the TAM phenotype as well as the protein expression of prospero homeobox1(PROX1)/interferon-γ(IFN-γ)of transplanted tumor.The effect of supernatant of gastric cancer cell intervened by Hewei Xiaoliu Formula on TAM phenotype was detected by flow cytometry.Enzyme linked immunosorbent assay(ELISA)and Western blot were used to detect the effect of Hewei Xiaoliu Formula on the expression of IFN-γ in the supernatant of gastric cancer cells and protein expression of PROX1/IFN-γ in gastric cancer cells.Co-culture system of macrophages and gastric cancer cells transfected with small interfering RNA(siR)-IFN-γ were established,and the phenotypic changes of TAM were detected after the intervention with Hewei Xiaoliu Formula.[Results]Hewei Xiaoliu Formula could reduce the volume and weight of transplanted tumor(P＜0.05),increase the proportion of M1 TAM and decrease the proportion of M2 TAM in tumor tissue(P＜0.05),decrease the expression of PROX1 protein and increase the expression of IFN-γ(P＜0.01).After the intervention of Hewei Xiaoliu Formula,the gastric cancer supernatant could increase the proportion of M1 TAM and decrease the proportion of M2 TAM(P＜0.01).Hewei Xiaoliu Formula could increase the expression of IFN-γ in the supernatant of gastric cancer(P＜0.05),decrease the expression of PROX1 protein(P＜0.05),and increase the expression of IFN-γ protein in gastric cancer cells(P＜0.05).In addition,after siR-IFN-γ transfection into gastric cancer cells,the proportion of M1 TAM after intervention with Hewei Xiaoliu Formula was lower than that in siR-negative control(NC)+Hewei Xiaoliu Formula group(P＜0.05).[Conclusion]Hewei Xiaoliu Formula can inhibit the growth of HGC-27 gastric cancer and promote the polarization of TAM to M1 phenotype in tumor microenvironment.The mechanism may be related to the regulation of PROX1/IFN-γsignaling pathway and the increase of IFN-γ expression in gastric cancer.
