Journal of ethnopharmacology · 2025
Wumei Wan remodels the tumor immune microenvironment via the Ido1-KYN-AHR axis in AOM/DSS-induced colorectal cancer model.
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Zhang Yi-Lin, Yang Ming-Jie, Yang Shu-Sen, Liu Yu-Shan, Jia Rui, Zhang Xin-Yue, Li Jing-Tao, Yan Shu-Guang
Аннотация
BACKGROUND: Colorectal cancer(CRC) is a prevalent malignancy of the digestive tract, with poor prognosis in advanced stages due to metastasis and immune evasion. Chronic intestinal inflammation is increasingly recognized as a key driver of CRC progression by disrupting the immune microenvironment.Wumei Wan(WMW),a traditional Chinese herbal formula,has shown anti-inflammatory efficacy in ulcerative colitis,but its potential to inhibit CRC and modulate the immune microenvironment remains unclear.
AIM: This study aims to determine whether WMW can ameliorate CRC progression and to investigate the underlying mechanisms involved.
METHODS: An azoxymethane/dextran sulfate sodium(AOM/DSS)-induced CRC mouse model was established. Integrated transcriptomics, metabolomics,and network pharmacology analyses were employed to elucidate and validate the mechanisms of WMW.
RESULTS: WMW significantly suppressed CRC progression in mice,as demonstrated by improved colonic histology, lower Disease Activity Index(DAI) scores, increased survival rate,and reduced tumor burden.Mechanism analysis showed that WMW inhibited the IDO1-KYN-AHR pathway, reduced Th17 and Treg cell proliferation and differentiation, restored CD8+T cell function,and enhanced antitumor immunity.
CONCLUSION: This study demonstrates that WMW may suppress CRC progression by inhibiting the IDO1-KYN-AHR signaling pathway, reducing Th17 and Treg cell activity,and enhancing antitumor immune responses.Further studies are required to confirm the causal relationship of the IDO1-KYN-AHR axis in CRC progression.
AIM: This study aims to determine whether WMW can ameliorate CRC progression and to investigate the underlying mechanisms involved.
METHODS: An azoxymethane/dextran sulfate sodium(AOM/DSS)-induced CRC mouse model was established. Integrated transcriptomics, metabolomics,and network pharmacology analyses were employed to elucidate and validate the mechanisms of WMW.
RESULTS: WMW significantly suppressed CRC progression in mice,as demonstrated by improved colonic histology, lower Disease Activity Index(DAI) scores, increased survival rate,and reduced tumor burden.Mechanism analysis showed that WMW inhibited the IDO1-KYN-AHR pathway, reduced Th17 and Treg cell proliferation and differentiation, restored CD8+T cell function,and enhanced antitumor immunity.
CONCLUSION: This study demonstrates that WMW may suppress CRC progression by inhibiting the IDO1-KYN-AHR signaling pathway, reducing Th17 and Treg cell activity,and enhancing antitumor immune responses.Further studies are required to confirm the causal relationship of the IDO1-KYN-AHR axis in CRC progression.