Effects of astragaloside Ⅳ on low-glucose mediated tumor immuno-suppression microenvironment and its mechanism
10.12092/j.issn.1009-2501.2024.11.001
- VernacularTitle:黄芪甲苷Ⅳ干预低糖介导的肿瘤免疫抑制微环境作用及其机制研究
- Author:
Shiwen HUANG
1
;
Xiaohan SHAO
;
Xue ZHANG
;
Xinyi ZHU
;
Jingjing HAN
;
Mengting CUI
;
Fang LIU
;
Fangtian FAN
Author Information
1. 南京中医药大学中医学院,南京 210023,江苏
- Publication Type:Journal Article
- Keywords:
tumor-infiltrating lymphocytes;
As-Ⅳ;
low-glucose tumor microenvironment;
immuno-suppression
- From:
Chinese Journal of Clinical Pharmacology and Therapeutics
2024;29(11):1201-1211
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To investigate the effect of As-tragaloside Ⅳ(As-Ⅳ)on low-glucose mediated tu-mor immunosuppression microenvironment and its molecular mechanism.METHODS:MTT assay was used to detect the effect of As-Ⅳ on the prolifera-tion of CD4+T cells in low-glucose microenviron-ment in vitro.By ELISA experiment and qPCR detec-tion of interleukin 2(IL-2),interferon-gamma(IFN-γ),CD40L and transforming growth factor beta 1(TGF-β1)level;Western blot was used to detect the expression of glucose transporter 1(Glut-1),key glycolytic enzymes(HK,PFK1 and PK),AKT/mTOR signaling pathway and AKT/GSK3β signaling pathway in CD4+T cells.Molecular docking and AKT inhibitor experiments were used to verify the re-sults.B16-PKM2-OE was used to establish a low-glucose tumor microenvironment animal model for verification.RESULTS:MTT assay showed that As-Ⅳ promoted the proliferation of CD4+T cells in low-glucose microenvironment(P＜0.05).The results of ELISA and qPCR experiments showed that As-Ⅳcould increase the levels of IL-2,IFN-γ and CD40L,and reduce the level of TGF-β1 in tumor tissues(P＜0.05).Western blot results showed that As-Ⅳ pro-moted Glut-1 protein expression on the surface of CD4+T cells,up-regulated the expression of glycoly-sis key enzymes,and activated AKT/mTOR and AKT/GSK-3β signaling in a concentration-dependent manner.Molecular docking and join AKT inhibitors As the experiment results indicate-Ⅳ activated AKT/mTOR signaling and AKT/GSK-3β signal;Animal experiments showed that As-Ⅳ exerted anti-tumor effect by activating the proliferation and activation of CD4+T cells in low-glucose microenvironment.CONCLUSION:As-Ⅳ promote sugar by activation of AKT/Glut signal micro environment of CD4+T cell proliferation and activation play a role of anti-tu-mor.
