Lu Zhang, Songyu Liu, Kai Ding, Bin Zeng, Bo Li, Jinyi Zhou, Jv Li, Junliang Wang, Xiaosan Su, Ruifen Sun
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引用次数: 0
Abstract
Ethnopharmacological relevance: Positive deficiency and cancer toxicity are the main pathogenesis of colorectal cancer (CRC) lung metastasis. Yanghe decoction (YHD), a traditional Chinese medicine, has the effects of warming yang, tonifying blood, dispersing cold and clearing stagnation, adopting a treatment method that combines supporting the right and dispelling the wrong, which has remarkable efficacy in anti-tumor.Although, its precise mechanism of inhibiting the metastasis of colorectal cancer to the lung is still poorly understood.
Aim of the study: This study aimed to elucidate the antitumor properties of YHD within the context of colorectal cancer lung metastasis.
Materials and methods: Ultrahigh-performance liquid chromatography coupled with mass spectrometry (UHPLC-MS) was utilized to analyze the chemical composition of YHD. The anticancer activity of YHD was evaluated in a CRC lung metastasis mouse model by quantifying pulmonary metastatic nodules. The effects of YHD on CRC cell proliferation, apoptosis, cell cycle progression, and invasion were assessed using CCK-8 assays, flow cytometry, and Transwell assays. YHD-mediated immune modulation in tumor-bearing mice was evaluated by analyzing antitumor immunity, immunosuppressive cells, and cytokines in peripheral blood and tumor tissue. Gut microbiota analysis was conducted to determine the impact of YHD on the gut microbiota in mice.
Results: Our analysis identified 1801 chemical markers in YHD. CFA exacerbated lung metastasis in CRC, whereas oral administration of YHD significantly mitigated this effect, as evidenced by the reduced number of metastatic lung nodules in CRC tumor-bearing mice. In vitro experiments demonstrated that YHD inhibits CRC cell proliferation, induces apoptosis, and suppresses invasion. In the lung tissues of mice with CRC metastasis treated with CFA, there was a significant reduction in NK cells and IL-21, along with an increase in M2 macrophages and IL-6. Following YHD treatment, there was a notable increase in NK cells and IL-21, accompanied by a decrease in M2 macrophages and IL-6 in lung tissues. YHD administration was also associated with an increase in beneficial bacterial species such as Bacillus and a decrease in deleterious bacterial species such as Oscillibacter.
Conclusion: Our findings demonstrate that YHD inhibits lung metastasis in CRC by suppressing CRC cell proliferation and invasion, in addition to modulating the tumor microenvironment to favor antitumor immunity. These results provide a scientific basis for the clinical application of YHD in the treatment of CRC patients.
期刊介绍:
The Journal of Ethnopharmacology is dedicated to the exchange of information and understandings about people''s use of plants, fungi, animals, microorganisms and minerals and their biological and pharmacological effects based on the principles established through international conventions. Early people confronted with illness and disease, discovered a wealth of useful therapeutic agents in the plant and animal kingdoms. The empirical knowledge of these medicinal substances and their toxic potential was passed on by oral tradition and sometimes recorded in herbals and other texts on materia medica. Many valuable drugs of today (e.g., atropine, ephedrine, tubocurarine, digoxin, reserpine) came into use through the study of indigenous remedies. Chemists continue to use plant-derived drugs (e.g., morphine, taxol, physostigmine, quinidine, emetine) as prototypes in their attempts to develop more effective and less toxic medicinals.