Immunohistochemical analyses reveal FoxP3 expressions in spleen and colorectal cancer in mice treated with AOM/DSS, and their suppression by glycyrrhizin

Guifeng Wang ¹, Keiichi Hiramoto ², Ning Ma ^3,4

⁰Department of Acupuncture and Moxibustion Medical Science, Suzuka University of Medical Science, Suzuka, Mie, Japan.

Plos One +

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August 16, 2024

View abstract on PubMed

Summary

Glycyrrhizin (GL) reduces colorectal cancer (CRC) by decreasing regulatory T cells (Tregs) in the spleen. GL suppresses inflammation-related carcinogenesis and may inhibit cancer cell malignant transformation.

Area Of Science

Immunology
Oncology
Pharmacology

Background

Glycyrrhizin (GL) previously showed anti-inflammatory and anti-carcinogenic effects in a colorectal cancer (CRC) mouse model.
Regulatory T cells (Tregs) accumulation in the spleen was observed in this CRC model.

Purpose Of The Study

To investigate the role of splenic regulatory T cells (Tregs) in inflammation-related colorectal cancer (CRC) development.
To determine the effect of glycyrrhizin (GL) on Treg accumulation and its impact on colorectal cancer (CRC) progression.

Main Methods

Utilized an azoxymethane (AOM)/dextran sodium sulfate (DSS) induced murine model of colorectal cancer (CRC).
Administered glycyrrhizin (GL) to different treatment groups (Control, GL, CC, CC+GL).
Analyzed spleen weight, splenic tissue histology (white/red pulp), and quantified immune cell populations (Tregs, CTLs, dendritic cells) in spleen and colorectal tissues.

Main Results

Colorectal cancer (CC) group exhibited significant increases in spleen weight and Treg populations compared to controls.
GL administration significantly attenuated the increase in spleen weight and Treg accumulation.
GL treatment suppressed the increase in splenic Tregs and showed a trend towards increased cytotoxic T lymphocytes (CTLs).
Forkhead box protein 3 (FoxP3) expression was observed in colorectal cancer cells, suggesting a role in malignant transformation.

Conclusions

Accumulation of splenic regulatory T cells (Tregs) may promote inflammation-related colorectal cancer (CRC) by suppressing cytotoxic T lymphocytes (CTLs).
Glycyrrhizin (GL) suppresses colorectal cancer (CRC) development, potentially by reducing splenic Treg populations and inhibiting high-mobility group box 1 (HMGB1).
The expression of FoxP3 in cancer cells indicates a potential role in malignant transformation, warranting further investigation.