Treatment of cancer-associated fibroblast-like cells with celecoxib enhances the anti-cancer T helper 1/Treg responses in breast cancer

被引：1

作者：

Samoudi, Arash ^{[1
]}

Abolhasani-Zadeh, Firoozeh ^{[2
]}

Afgar, Ali ^{[3
]}

Jalilian, Elnaz ^{[1
]}

Zeinalynezhad, Hamid ^{[2
]}

Langroudi, Ladan ^{[1
]}

机构：

[1] Kerman Univ Med Sci, Sch Med, Dept Med Immunol, Pajoohesh Sq, Kerman 7616914111, Iran

[2] Kerman Univ Med Sci, Sch Med, Dept Surg, Kerman, Iran

[3] Kerman Univ Med Sci, Res Ctr Hydatid Dis Iran, Kerman, Iran

来源：

NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY | 2025年 / 398卷 / 05期

关键词：

Tumor microenvironment; Cancer-associated fibroblasts; Cycloxygenase-2; Celecoxib; Immunotherapy; TUMOR-ASSOCIATED MACROPHAGES; PROSTAGLANDIN E-2; DENDRITIC CELLS; EXPRESSION; COX-2; CYCLOOXYGENASE-2; INHIBITOR; PGE(2); PROLIFERATION; INFLAMMATION;

D O I：

10.1007/s00210-024-03641-3

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Tumor inflammation, as one of the hallmarks of cancer, has been the target for anti-cancer treatments. Celecoxib is a selective inhibitor of the enzyme cycloxygenase-2 (COX-2) and inhibits the production of PGE2, which is an important mediator of tumor inflammation produced by cancer cells and cells of the tumor microenvironment. In this study, we aimed at inhibiting COX-2 using celecoxib, expressed in cancer-associated fibroblast (CAF)-like cells isolated from breast cancer and evaluated the alterations in their cytokine profile and gene expression. CAF-like cells were isolated by explant culture from 13 breast cancer tissues. Simultaneously, peripheral blood mononuclear cells (PBMCs) were isolated from patients' blood. CAF-like cells were treated with 10 mu M of celecoxib and expression of genes COX-2, smooth muscle actin-alpha (alpha-SMA), and production of prostaglandin E2 (PGE2), Interleukin 10 (IL10), and transforming growth factor beta1 (TGF-beta 1) was evaluated. Next, PBMCs were co-cultured with celecoxib-treated CAF-like cells and the expression of genes T-bet, Foxp3, GATA-3; production of cytokines IFN-gamma, IL-10, IL-4, TGF-beta 1, and the mediator PGE2 were assessed by real-time-PCR and ELISA, respectively. Isolated CAF-like cells showed expression of fibroblast activation protein (FAP). Treatment with celecoxib was able to efficiently reduce the production of PGE2 and the expression of alpha-SMA in isolated CAF-like cells. Furthermore, PBMCs in co-culture with these cells showed enhanced Th1 phenotype including T-bet and IFN gamma expression and decreased the phenotypical markers of regulatory T cells such as FoxP3 and IL-10 and TGF-beta 1 production. Our study shows the important role of COX-2 in CAFs by promoting immune suppression. Our results suggested that high expression of COX-2 in CAFs may serve as a new therapeutic, targeting CAFs in enhancing immune responses in breast cancer treatment.

引用

页码：6099 / 6112

页数：14

共 68 条

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