中国癌症防治杂志2025，Vol.17Issue(6)：715-721,7.DOI:10.3969/j.issn.1674-5671.2025.06.09
美雌醇通过促进AGK表达增强CD8+T细胞效应功能
Mestranol enhances CD8+T cell effector functions by promoting expression of AGK
摘要
Abstract
Objective To investigate the transcriptional activation potential of Mestranol(Mes)on acylglycerol Kinase(AGK)and its role in enhancing CD8+T cell effector function.Methods Public databases were utilized to analyze the correlation between AGK expression and CD8+T cell effector function genes,and its association with CD8+T cell infiltration levels across the tumor microenvi-ronments.The effects of Mestranol on AGK mRNA and protein expression levels,as well as on the activation of the AGK downstream signaling pathway were assessed using quantitative PCR(qPCR)and Western blot.The half maximal inhibitory concentration(IC50)of Mestranol was determined using the CCK-8 assay.An AGK overexpression plasmid was transfected into human T lymphocyte leukemia Jurkat cells and CD8⁺ T cells by electroporation,and a luciferase reporter gene assay was employed to examine the impact of Mestranol on AGK promoter transcriptional activity.Enzyme-linked immunosorbent assay(ELISA)was used to quantify the levels of interferon-γ(IFN-γ)and tumor necrosis factor-α(TNF-α)secreted by CD8+T cells under following AGK overexpression,along with Mestranol's effects on these parameters.The effects of Mestranol on the cytotoxic activity of CD8+T cells was assessed in vitro using flow cytometry.Results Public databases analysis revealed that AGK expression was significantly positively correlated with CD8+T cell effector function genes,negatively correlated with inhibitory function genes,and positively associated with CD8+T cell infiltration levels in various tumor microenvironments(all P<0.05).The IC50 of Mestranol was 36 μmol/L.Mestranol significantly upregulated AGK expression at both mRNA and protein levels in Jurkat cells in a dose-dependent manner across various concentrations(all P<0.01).Furthermore,luciferase reporter assays demonstrated that Mestranol significantly enhanced the transcriptional activity of the AGK promoter(P<0.001).Mestranol elevated the phosphorylation levels of AKT protein at Ser473,enhanced the secretion of IFN-γ and TNF-α in treated CD8⁺T cells(all P<0.001),and increased their tumor-killing capacity in vitro(P<0.01).Conclusions Mestranol up-regulates AGK expression by enhancing the transcriptional activity of the AGK promoter,thereby augmenting CD8+T cell effector function,which provides a new insight for tumor immunotherapy targeting AGK.关键词
美雌醇/酰基甘油激酶/CD8+T细胞/肿瘤免疫Key words
Mestranol/Acylglycerol kinase/CD8+T cell/Tumor immunity分类
医药卫生引用本文复制引用
禚方圻,车永胜,徐小洁,王瑞琨,武广隆,韩聚强,王晓宇,徐凯月,刘思含,肖晓依楠,杜祎萌..美雌醇通过促进AGK表达增强CD8+T细胞效应功能[J].中国癌症防治杂志,2025,17(6):715-721,7.基金项目
国家重点研发计划项目(2023YFA0914900) （2023YFA0914900）
国家自然科学基金青年科学基金项目(82404651) （82404651）
北京市自然科学基金-昌平创新联合基金项目(L234042) （L234042）
