What question did this study set out to answer?

This research aims to evaluate the efficacy of Thlaspi arvense in preventing colorectal cancer linked to colitis and understand its underlying mechanisms.

April 19, 2026Open Access

Thlaspi arvense attenuates colitis-associated colorectal tumorigenesis through suppression of neutrophil recruitment via the NOD/NF-κB pathway

Key Points

This research aims to evaluate the efficacy of Thlaspi arvense in preventing colorectal cancer linked to colitis and understand its underlying mechanisms.
Used an AOM/DSS mouse model of colitis-associated colorectal cancer.
Administered Thlaspi arvense to assess effects on tumorigenesis and inflammation severity.
Conducted histological analysis on mucosal integrity and protein expression.
Measured neutrophil recruitment and cytokine levels using flow cytometry and ELISA.
Explored molecular mechanisms through RNA sequencing and Western blot analysis.
Thlaspi arvense treatment significantly decreased body weight loss and adenoma formation in mice.
Restored mucosal integrity by increasing tight junction proteins ZO-1 and Claudin-1 expression.
Reduced levels of neutrophil chemoattractants CXCL1 and CXCL2, resulting in decreased neutrophil recruitment.
Inhibited the NOD/NF-κB pathway, impacting neutrophil-driven inflammation and tumor microenvironment.

Abstract

Abstract Background In colitis-associated colorectal cancer (CAC), chronic inflammation is the primary driver of tumorigenesis. A critical event in this process is the massive recruitment of neutrophils, which, while part of the host defense, can paradoxically fuel cancer progression. Excessive neutrophil infiltration contributes to sustained mucosal damage through the release of pro-inflammatory mediators and shapes a tumor-promoting microenvironment. Despite their recognized role, therapeutic strategies specifically targeting pathogenic neutrophil recruitment in CAC are limited. Thlaspi arvense (TA), a traditional medicinal plant, possesses purported anti-inflammatory properties, suggesting its potential utility against CAC. Therefore, this study was designed to evaluate the efficacy of TA in preventing CAC and to delineate its mechanism of action, particularly its impact on neutrophil-driven inflammation. Methods An azoxymethane/dextran sulfate sodium (AOM/DSS) mouse model of CAC was employed. Mice were administered with TA to evaluate its effects on disease severity, as gauged by body weight change, colon length, tumor burden, and survival rate. Histological and immunofluorescence staining were performed to assess mucosal integrity and the expression of tight junction proteins (ZO-1, Claudin-1). Neutrophil infiltration was quantified by flow cytometry and immunofluorescence. The levels of pro-inflammatory cytokines (IL-6, TNF-α, IL-1β, IFN-γ) and neutrophil chemoattractants (CXCL1/2) were measured using ELISA and qPCR, respectively. To specifically probe the CXCL1/2-CXCR2 axis, a CXCR2 inhibitor was used as an interventional control. Mechanistic insights were gained through RNA sequencing and Western blot analysis. Furthermore, molecular docking was performed to predict the binding affinity of key TA constituents to core proteins within the NOD/NF-κB pathway. Results The AOM/DSS mouse model successfully recapitulated the hallmark features of CAC. Treatment with TA, especially at higher doses, markedly attenuated the pathological manifestations, including body weight loss, colon shortening, adenoma formation, and severe inflammatory responses. Consistently, the TA administration restored mucosal integrity and significantly upregulated the expression of tight junction proteins ZO-1 and Claudin-1. At a functional level, TA significantly reduced the production of the neutrophil chemoattractants CXCL1 and CXCL2, which and consequently impaired the interaction with CXCR2 on neutrophils and led to a substantial decrease in neutrophil recruitment. Mechanistic investigation further demonstrated that TA exerted its effects by suppressing the activation of key proteins within the NOD/NF-κB signaling pathway. This suppression resulted in diminished CXCL1/2 expression and a consequent attenuation of the neutrophil-driven pro-tumorigenic microenvironment. Conclusions We conclude that TA attenuates colitis-associated carcinogenesis by inhibiting the NOD/NF-κB pathway and its downstream CXCL1/2-CXCR2-mediated neutrophil recruitment. This study underscores the value of targeting neutrophil-driven inflammation and positions TA as a viable natural therapeutic for preventing CAC progression. Graphical Abstract

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