Integrative analysis and identification of key elements and pathways regulated by Traditional Chinese Medicine (Yiqi Sanjie formula) in colorectal cancer

Abstract

Introduction: The clinical efficacy of Yiqi Sanjie (YQSJ) formula in the treatment of stage III colorectal cancer (CRC) has been demonstrated. However, the underlying antitumor mechanisms remain poorly understood.Materials and methods: The aim of the present study was to comprehensively characterize the molecular and microbiota changes in colon tissues and fecal samples from CRC mice and in CRC cell lines treated with YQSJ or its main active component, peiminine. Integrative tandem mass tag-based proteomics and ultra-performance liquid chromatography coupled with time-of-flight tandem mass spectrometry metabolomics were used to analyze azoxymethane/dextran sulfate sodium-induced CRC mouse colon tissues.Results: The results showed that 0.8% (57/7568) of all detected tissue proteins and 3.2% (37/1141) of all detected tissue metabolites were significantly changed by YQSJ treatment, with enrichment in ten and six pathways associated with colon proteins and metabolites, respectively. The enriched pathways were related to inflammation, sphingolipid metabolism, and cholesterol metabolism. Metabolomics analysis of fecal samples from YQSJ-treated mice identified 121 altered fecal metabolites and seven enriched pathways including protein digestion and absorption pathway. 16S rRNA sequencing analysis of fecal samples indicated that YQSJ restored the CRC mouse microbiota structure by increasing the levels of beneficial bacteria such as Ruminococcus_1 and Prevotellaceae_UCG_001. In HCT-116 cells treated with peiminine, data-independent acquisition-based proteomics analysis showed that 1073 of the 7152 identified proteins were significantly altered and involved in 33 pathways including DNA damage repair, ferroptosis, and TGF-β signaling.Conclusion: The present study identified key regulatory elements (proteins/metabolites/bacteria) and pathways involved in the antitumor mechanisms of YQSJ, suggesting new potential therapeutic targets in CRC.

Meta‐analysis on the efficacy of Traditional Chinese Medicine in enhancing surgical site wound healing post‐colorectal surgery

“…This could potentially be attributed to the properties of TCM formulations in modulating molecular and microbiota changes in CRC tissues, thereby suggesting new potential therapeutic targets in CRC. 12 Recent studies have highlighted the promising role of TCM formulations in mitigating the complications associated with colorectal surgeries and improving the outcomes in CRC patients. For instance, the Insect Compound Particle (CYFF), a TCM compound, has been noted for its potential in reducing the toxicity associated with CRC chemotherapy and enhancing the anti‐tumour effect, although high‐quality clinical evidence remains to be established.…”

“…The significant reduction in the REEDA scale scores in the TCM‐treated groups at both the 10th day and 1‐month post‐surgery intervals indicates a faster and more efficient wound healing process. This could potentially be attributed to the properties of TCM formulations in modulating molecular and microbiota changes in CRC tissues, thereby suggesting new potential therapeutic targets in CRC 12 . Recent studies have highlighted the promising role of TCM formulations in mitigating the complications associated with colorectal surgeries and improving the outcomes in CRC patients.…”

“…14 Furthermore, the Yiqi Sanjie (YQSJ) formula has demonstrated clinical efficacy in the treatment of stage III CRC, with studies illustrating its role in modulating molecular and microbiota changes in CRC tissues and cell lines, thereby suggesting new potential therapeutic targets in CRC. 12 Moreover, the integration of TCM factors in prognostic models, leveraging machine learning methods, has shown promise in predicting the recurrence and metastasis in stage I-III CRC patients, thereby offering a novel approach in the clinical management of CRC. 15 The TTT surgery, an extension of the Ilizarov technique, has been combined with TCM approaches to alleviate ischemic symptoms and enhance wound healing.…”

A novel miR-490-3p/hnRNPA1-b/PKM2 axis intermediates the Warburg effect and proliferation of colon cancer via PI3K/AKT pathway

“…After treatment with Yi Qi Dispersal Formula, the level of hnRNPA1 significantly decreased. The differential protein KEGG analysis and PI3K/AKT signaling pathway showed a close relationship between the two groups (Wan et al 2022).…”

Elucidation of the mechanism of action of ailanthone in the treatment of colorectal cancer: integration of network pharmacology, bioinformatics analysis and experimental validation

“…Currently, surgery, chemotherapy, radiotherapy, and biotherapy are commonly employed for CRC treatment. However, they pose challenges such as low target specificity, toxic side effects, heavy economic burden, and poor patient compliance, often leading to treatment discontinuation or poor efficacy ( Yaghoubi et al, 2020 ; Wan et al, 2022 ). Active ingredients in traditional Chinese medicine offer early treatment responses, symptom improvement, prolonged survival, immune function regulation, and enhanced quality of life for patients with CRC ( Guo et al, 2012 ; Li et al, 2021b ).…”