Integrative analysis and identification of key elements and pathways regulated by Traditional Chinese Medicine (Yiqi Sanjie formula) in colorectal cancer.
Integrative analysis and identification of key elements and pathways regulated by Traditional Chinese Medicine (Yiqi Sanjie formula) in colorectal cancer.
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大肠癌中中医（Yiqi Sanjie配方）调节的关键要素和途径的综合分析和识别。
DOI：
10.3389/fphar.2022.1090599
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发表时间：
2022
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
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作者：
前言：益气散结方治疗III期结直肠癌的临床疗效已得到证实。然而，潜在的抗肿瘤机制仍然知之甚少。 材料与方法：本研究的目的是全面表征结直肠癌小鼠的结肠组织和粪便样品中的分子和微生物群变化，以及用YQSJ或其主要活性成分贝母素处理的结直肠癌细胞系。采用基于整合串联质谱标签的蛋白质组学和超高效液相色谱-飞行时间串联质谱代谢组学分析氧化偶氮甲烷/葡聚糖硫酸钠诱导的CRC小鼠结肠组织。 结果如下：结果表明，YQSJ处理后，0.8%（57/7568）的所有检测到的组织蛋白和3.2%（37/1141）的所有检测到的组织代谢物发生了显著变化，分别富集了与结肠蛋白和代谢物相关的10条和6条途径。富集的途径与炎症、鞘脂代谢和胆固醇代谢有关。对YQSJ处理小鼠的粪便样品进行代谢组学分析，鉴定出121种改变的粪便代谢物和7种富集途径，包括蛋白质消化和吸收途径。粪便样品的16 S rRNA测序分析表明，YQSJ通过增加有益细菌如Ruminococcus_1和Prevotellaceae_UCG_001的水平来恢复CRC小鼠微生物群结构。在用贝母素处理的HCT-116细胞中，基于数据独立采集的蛋白质组学分析显示，在7152个鉴定的蛋白质中，有1073个发生了显著改变，涉及33条途径，包括DNA损伤修复，铁凋亡和TGF-β信号转导。 结论：本研究确定了参与YQSJ抗肿瘤机制的关键调控元件（蛋白质/代谢产物/细菌）和途径，提示了CRC的新的潜在治疗靶点。
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.
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影响因子：
--
作者：
El Bali M;Bakkach J;Bennani Mechita M
通讯作者：
Bennani Mechita M
影响因子：
5.6
作者：
Heinrich, Michael;Jalil, Banaz;Abdel-Tawab, Mona;Echeverria, Javier;Kulic, Zarko;McGaw, Lyndy J.;Pezzuto, John M.;Potterat, Olivier;Wang, Jia-Bo
通讯作者：
Wang, Jia-Bo
影响因子：
64.5
作者：
FISHEL, R;LESCOE, MK;KOLODNER, R
通讯作者：
KOLODNER, R
影响因子：
3.6
作者：
Ryland, Lindsay K.;Fox, Todd E.;Kester, Mark
通讯作者：
Kester, Mark
影响因子：
254.7
作者：
Ciardiello, Fortunato;Ciardiello, Davide;Cervantes, Andres
通讯作者：
Cervantes, Andres