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Exploring the Anticancer Effects of Xianliu Jieduan Fang on Colitis-Associated Colorectal Cancer Through Network
Fang-Lan Li1, Bei-Bei Wang1, Ke-Feng Zeng2
1Department of Anorectal, Shenzhen Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, China.
Abstract:
This study evaluated the therapeutic effects of Xianliu Jieduan Fang (XLJDF) on colitis-associated colorectal cancer (CAC) and explored its molecular mechanisms through network pharmacology and experimental validation. Using an AOM/DSS-induced CAC mouse model, we evaluated XLJDF's efficacy. Active components were identified by UHPLC-QE-HRMS. Targets were predicted using SwissTargetPrediction and PubChem, while disease genes were obtained from GeneCards, DisGeNET, and TTD. Core targets and pathways were analyzed via Cytoscape and Metascape. Mechanisms were validated through molecular docking and experiments. XLJDF improved colon pathology and identified 68 active compounds, including nine key components like Kaempferol and Luteolin. Network analysis revealed 959 targets with 29 core genes (AKT1, CTNNB1, GSK3B, etc.). KEGG analysis showed XLJDF primarily acts through Wnt signaling, regulating apoptosis and cell migration. Experimental validation confirmed XLJDF inhibits Wnt/β-catenin pathway by preventing GSK3β inactivation. XLJDF exerts anti-CAC effects via a multi-component, multi-target network. Our study identifies key active compounds and demonstrates that XLJDF suppresses the Wnt/β-catenin pathway by preventing GSK3β inactivation, thereby inhibiting β-catenin stabilization.
Insights
Xianliu Jieduan Fang (XLJDF) effectively treats colitis-associated colorectal cancer (CAC) by targeting multiple molecular pathways. This traditional formula inhibits the Wnt/β-catenin signaling pathway, offering a novel therapeutic strategy for CAC.
Area of Science:
- Integrative oncology
- Pharmacology
- Molecular biology
Background:
- Colitis-associated colorectal cancer (CAC) presents a significant therapeutic challenge.
- Understanding the molecular mechanisms of traditional Chinese medicine (TCM) for CAC is crucial for developing novel treatments.
Purpose of the Study:
- To evaluate the therapeutic efficacy of Xianliu Jieduan Fang (XLJDF) on CAC.
- To elucidate the molecular mechanisms underlying XLJDF's anti-CAC effects using network pharmacology and experimental validation.
Main Methods:
- An AOM/DSS-induced CAC mouse model was employed for efficacy evaluation.
- Ultra-high-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UHPLC-QE-HRMS) identified active compounds.
- Network pharmacology (SwissTargetPrediction, PubChem, Cytoscape, Metascape) predicted targets and pathways.
- Molecular docking and experimental validation confirmed mechanisms.
Main Results:
- XLJDF treatment improved colon pathology in the CAC mouse model.
- Sixty-eight active compounds were identified, with Kaempferol and Luteolin being key components.
- Network analysis revealed 959 targets, including 29 core genes (e.g., AKT1, CTNNB1, GSK3B).
- XLJDF primarily modulates Wnt signaling, affecting apoptosis and cell migration.
- Experimental validation confirmed XLJDF inhibits the Wnt/β-catenin pathway by preventing GSK3β inactivation.
Conclusions:
- XLJDF exerts anti-CAC effects through a multi-component, multi-target mechanism.
- XLJDF suppresses the Wnt/β-catenin pathway by inhibiting GSK3β inactivation, thereby preventing β-catenin stabilization.
- This study provides a scientific basis for XLJDF as a potential therapeutic agent for CAC.
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