Phytomedicine : international journal of phytotherapy and phytopharmacology · 2026
Lichang decoction suppresses AOM+DSS-induced colitis-associated cancer via regulating intestinal flora and suppressing the Wnt/β-catenin signaling pathway.
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Xie Yimin, Lin Jinghong, Huang Zishan, Jiang Dongxu, Peng Linsi, Luo Yingtian, Liang Jian, Han Yun, Guo Shaoju, Jiang Xiaoyan
Аннотация
BACKGROUND: Lichang Decoction (LCD), a traditional Chinese medicine formula clinically used for intestinal disorders, has shown anti-inflammatory potential; however, its therapeutic efficacy and underlying mechanism in colitis-associated colorectal cancer (CAC) remain unclear.
PURPOSE: The objective of this study is to investigate the effects and mechanisms of LCD in an AOM+DSS-induced CAC mouse model.
METHODS: The primary constituents of LCD were analyzed using ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS). An azoxymethane/dextran sulfate sodium (AOM+DSS)-induced CAC mouse model was established and treated with low- or high-dose LCD, or 5-fluorouracil (5-Fu). Clinical symptoms, tumor burden, histopathological changes and inflammatory responses were evaluated. Intestinal barrier integrity was assessed by tight junction and mucus-related markers. Transcriptomic analysis, quantitative PCR and Western blotting were performed to investigate the Wnt/β-catenin signaling pathway. Gut microbiota alterations were analyzed by 16S rRNA sequencing, and fecal microbiota transplantation (FMT) was conducted to determine the causal role of microbiota in LCD-mediated protection.
RESULTS: LCD treatment significantly alleviated weight loss, diarrhea and hematochezia, reduced disease activity index scores, and markedly suppressed tumor number and size in CAC mice. LCD attenuated colonic inflammation by decreasing serum and tissue levels of IL-1β, TNF-α, IL-6 and IFN-γ, while reducing CD11b⁺ and MPO⁺ inflammatory cell infiltration. Moreover, LCD restored intestinal barrier function and increased goblet cell abundance. Mechanistically, transcriptomic, molecular analyses and molecular docking revealed that LCD significantly inhibited aberrant activation of the Wnt/β-catenin pathway, evidenced by reduced expression of Wnt4, β-catenin, c-Myc and cyclin D1. However, LCD treatment in HCT116 cells did not affect the Wnt/β-catenin pathway. Additionally, LCD reshaped gut microbiota composition by suppressing tumor-associated bacterial taxa (Bacillota and Bacteroidota) and enriching beneficial Verrucomicrobiota. Correlation and functional prediction analyses linked microbial modulation to Wnt/β-catenin signaling and tumor progression. Importantly, FMT derived from LCD exerted an inhibitory effect on tumor progression in pseudo-germ-free CAC mice, but direct administration of LCD in pseudo-germ-free CAC mouse model did not demonstrate a significant tumor-suppressive effect.
CONCLUSION: LCD effectively suppresses CAC by remodeling gut microbiota to inhibit Wnt/β-catenin signaling, thereby alleviating inflammation, restoring intestinal barrier function and restraining tumor progression. These findings indicate that LCD represents a viable therapeutic intervention for CAC treatment.
PURPOSE: The objective of this study is to investigate the effects and mechanisms of LCD in an AOM+DSS-induced CAC mouse model.
METHODS: The primary constituents of LCD were analyzed using ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS). An azoxymethane/dextran sulfate sodium (AOM+DSS)-induced CAC mouse model was established and treated with low- or high-dose LCD, or 5-fluorouracil (5-Fu). Clinical symptoms, tumor burden, histopathological changes and inflammatory responses were evaluated. Intestinal barrier integrity was assessed by tight junction and mucus-related markers. Transcriptomic analysis, quantitative PCR and Western blotting were performed to investigate the Wnt/β-catenin signaling pathway. Gut microbiota alterations were analyzed by 16S rRNA sequencing, and fecal microbiota transplantation (FMT) was conducted to determine the causal role of microbiota in LCD-mediated protection.
RESULTS: LCD treatment significantly alleviated weight loss, diarrhea and hematochezia, reduced disease activity index scores, and markedly suppressed tumor number and size in CAC mice. LCD attenuated colonic inflammation by decreasing serum and tissue levels of IL-1β, TNF-α, IL-6 and IFN-γ, while reducing CD11b⁺ and MPO⁺ inflammatory cell infiltration. Moreover, LCD restored intestinal barrier function and increased goblet cell abundance. Mechanistically, transcriptomic, molecular analyses and molecular docking revealed that LCD significantly inhibited aberrant activation of the Wnt/β-catenin pathway, evidenced by reduced expression of Wnt4, β-catenin, c-Myc and cyclin D1. However, LCD treatment in HCT116 cells did not affect the Wnt/β-catenin pathway. Additionally, LCD reshaped gut microbiota composition by suppressing tumor-associated bacterial taxa (Bacillota and Bacteroidota) and enriching beneficial Verrucomicrobiota. Correlation and functional prediction analyses linked microbial modulation to Wnt/β-catenin signaling and tumor progression. Importantly, FMT derived from LCD exerted an inhibitory effect on tumor progression in pseudo-germ-free CAC mice, but direct administration of LCD in pseudo-germ-free CAC mouse model did not demonstrate a significant tumor-suppressive effect.
CONCLUSION: LCD effectively suppresses CAC by remodeling gut microbiota to inhibit Wnt/β-catenin signaling, thereby alleviating inflammation, restoring intestinal barrier function and restraining tumor progression. These findings indicate that LCD represents a viable therapeutic intervention for CAC treatment.