황금탕이 대장염과 관련된 대장암의 대사 안정성 조절 작용

  • role: First author第一作者
  • Affiliation:

    Heilongjiang University of Chinese Medicine, Harbin 150040,China

  • Email:18946239877@163.com
  • Introduction:E-mail18946239877@163.com
ZUO Xingbo1,  
  • Affiliation:

    Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China

FENG Xue2,  
  • Affiliation:

    Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China

ZHANG Caijuan2,  
  • Affiliation:

    Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China

LIU Haifan2,  
  • Affiliation:

    Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China

LIU Jianyao2,  
  • Affiliation:

    Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China

LIU Bin2,  
  • Affiliation:

    Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China

ZHU Lin2,  
  • Affiliation:

    Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China

SUN Qiyue2,  
  • role: Corresponding author通信作者
  • Affiliation:

    Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China

  • Email:wdf122644@126.com
  • Introduction:E-mailwdf122644@126.com
WANG Dunfang2*,  
  • role: Corresponding author通信作者
  • Affiliation:

    Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China

  • Email:wpyang@icmm.ac.cn
  • Introduction:E-mailwpyang@icmm.ac.cn
YANG Weipeng2*

추상적인

이 연구는 황금탕(HQT)이 대장염과 관련된 대장암(CAC)의 염종 전환 과정에서 대사 재구성을 조절하는 작용 메커니즘을 탐구하는 것을 목적으로 한다. 이를 위해 황금탕을 투여한 CAC 모델 마우스를 구축했으며, LC-MS/MS를 통한 타겟되지 않은 대사체계 및 다중통계 분석 방법을 사용하여 황금탕이 CAC 모델 마우스에서 대사 재구성에 미치는 영향을 평가하였다. 결과적으로 황금탕이 CAC 모델 마우스 내부의 주요 대사물질불균형을 현저하게 교정하는 효과가 있다. 정상모델군과 비교하면, 염종의 염증기, 증식기 및 종양형성기 단계에서 각각 52, 67, 45종의 대사물질의 차이가 나타났다. 이 중, 락토스, 리놀레산, 어린씨름산, 역어린씨름산 및 베타인은 대장암병의 특성적 대사물질로 대장염-암 전환 기간 동안 계속해서 풍부하게 나타난다. 대사물질의 차이로 보여진 경로들의 풍부함 분석 결과, 리놀레산 대사와 아라키돈산 대사는 CAC 발병에서 가장 크게 교란을 받는 대사경로였다. 증식단계는 아미노산 대사망의 확대로 나타났으며, 종양기에는 나이아신염과 나이아시나마이드 대사, 이노시톨 대사의 2개의 새로운 경로가 나타났다. 황금탕의 개입효과는 염증단계에서 아라키돈산 대사를 조절하는데 나타나며, 증식기에는 콜린-카니틴 대사 불균형을 교정하고, 종양기에는 나이아시나마이드 및 트립토판 대사를 억제하는데 중점을 둔다. 결론적으로 황금탕이 대장염-암 전환과정의 대사불균형을 효과적으로 교정함으로써 대장염으로부터의 암화 전환 과정을 효과적으로 지연시킨다. 또한 대장의 '염-암' 전환의 동적 대사특성을 밝혀냄으로써, 대사 재구성을 기반으로 한 중약의 항암 표적기제 연구에 새로운 제시를 제공한다.

키워드

황금탕; 암으로의 전환; 대사체계학; 염증; 증식

References

  1. 1.
    FERLAY J,STELIAROVA-FOUCHER E,LORTET-TIEULENT J,et al.Cancer incidence and mortality patterns in Europe:Estimates for 40 countries in 2012[J].Eur J Cancer,2013,49(6):1374-1403.
  2. 2.
    ANGELOU A,ANDREATOS N,ANTONIOU E,et al.A Novel modification of the AOM/DSS model for inducing intestinal adenomas in mice[J].Anticancer Res,2018,38(6):3467-3470.
  3. 3.
    CHEN X,HE S Q,LI W D.Effective therapeutic targets of traditional Chinese medicine for colorectal cancer based on its pathogenesis[J].World Chin Med,2023,18(21):3118-3124.
  4. 4.
    DEKKER E,TANIS P J,VLEUGELS J L A,et al.Colorectal cancer[J].Lancet,2019,394(10207):1467-1480.
  5. 5.
    YU F H,HUANG J,CHENG N,et al.Immune metabolic reprogramming:A new perspective of traditional Chinese medicine in the treatment of colon cancer[J].Jiangxi J Tradit Chin Med,2023,54(9):70-75.
  6. 6.
    NICOLINIA,FERRARIP.Involvement of tumor immune microenvironment metabolic reprogramming in colorectal cancer progression,immune escape,and response to immunotherapy[J].Front Immunol,2024,15:1353787.
  7. 7.
    WUZ D,ZUOM L,ZENGL,et al.OMA1 reprograms metabolism under hypoxia to promote colorectal cancer development[J].EMBO Rep,2021,22(1):e50827.
  8. 8.
    RADHAKRISHNAN S T,TRUST I C H N,MULLISH B H,et al.Deciphering the microbiome-metabolome landscape of an inflammatory bowel disease inception cohort[J].Gut Microbes,2025,17(1):2527863.
  9. 9.
    SIDEBOTTOM A M,CHANG E B.IBD microbial metabolome:The good,bad,and unknown[J].Trends Endocrinol Metab,2020,31(11):807-809.
  10. 10.
    ZAKERSKA-BANASZAK O,LADZIAK K,KRUSZKA D,et al.New potential biomarkers of ulcerative colitis and disease course:Integrated metagenomic and metabolomic analysis among Polish patients[J].J Gastroenterol,2025,doi:.
  11. 11.
    WANG D Z,DUBOIS R N.The role of anti-inflammatory drugs in colorectal cancer[J].Annu Rev Med,2013,64(1):131-144.
  12. 12.
    BERTAGNOLLI M M,EAGLE C J,ZAUBER A G,et al.Celecoxib for the prevention of sporadic colorectal adenomas[J].N Engl J Med,2006,355(9):873-884.
  13. 13.
    YI C Q,SUN J N,ZHANG J J,et al.Study on Sijunzi decoction in rectifying digestive disorder in mice[J].Chin J Integr Trad West Med,1997(1):42-44.
  14. 14.
    JIANG Y F,HUANG Y,XIAO C,et al.Inhibitory effect and mechanism of Sishenwan-containing serum on aerobic glycolysis in human colon cancer cells[J].Chin J Exp Tradit Med Form,2023,29(19):26-33.
  15. 15.
    LAMW,BUSSOMS,GUANF L,et al.The four-herb Chinese medicine PHY906 reduces chemotherapy-induced gastrointestinal toxicity[J].Sci Transl Med,2010,2(45):45ra59.
  16. 16.
    CHANGOUC A,SHIAHH S,CHENL T,et al.A phase Ⅱ clinical trial on the combination therapy of PHY906 plus capecitabine in hepatocellular carcinoma[J].The Oncologist,2021,26(3):e367-e373.
  17. 17.
    LIUS H,CHENGY C.Old formula,new Rx:The journey of PHY906 as cancer adjuvant therapy[J].J Ethnopharmacol,2012,140(3):614-623.
  18. 18.
    WANGD F,ZHUL,LIUH F,et al.Huangqin decoction alleviates colitis-associated colorectal cancer via amino acids homeostasis and PI3K/Akt/mTOR pathway modulation[J].J Ethnopharmacol,2024,334:118597.
  19. 19.
    MAX R,WANGD F,LIUY Q,et al.Transcriptomics and experimental validation-based approach to understand the effect and mechanism of Huangqin decoction interfeience with colitis associated colorectal cancer[J].Heliyon,2023,9(3):e13739.
  20. 20.
    ZHU L,WANG D F,FENG X,et al.Effect of huangqin decoction on inflammation and short-chain fatty acid-related gut microbiota in mouse model of inflammation-associated colorectal cancer[J].Chin J Exp Tradit Med Form,2024,30(23):157-169.
  21. 21.
    ZHU L,WANG D F,FENG X,et al.Intervention mechanism of Huangqintang on intestinal inflammation and proliferation in colitis-associated colon cancer[J].Chin J Exp Tradit Med Form,2023,29(22):1-10.
  22. 22.
    LI T,ZHUANG S X,WANG Y W,et al.Flavonoid profiling of a traditional Chinese medicine formula of Huangqin Tang using high performance liquid chromatography[J].Acta Pharm Sin B,2016,6(2):148-157.
  23. 23.
    THAKER A I,SHAKER A,RAO M S,et al.Modeling colitis-associated cancer with azoxymethane (AOM) and dextran sulfate sodium (DSS)[J].J Vis Exp,2012(67):4100.
  24. 24.
    WIRTZ S,POPP V,KINDERMANN M,et al.Chemically induced mouse models of acute and chronic intestinal inflammation[J].Nat Protoc,2017,12(7):1295-1309.
  25. 25.
    WANG D F,ZHU L,LIU H F,et al.Altered gut metabolites and metabolic reprogramming involved in the pathogenesis of colitis-associated colorectal cancer and the transition of colon "inflammation to cancer"[J].J Pharm Biomed Anal,2025,253:116553.
  26. 26.
    SUN R Q,ZHANG Y Y,ZHAO X,et al.Temporal and spatial metabolic shifts revealing the transition from ulcerative colitis to colitis-associated colorectal cancer[J].Adv Sci,2025,12(11):e2412551.
  27. 27.
    SUN Y D,HE Q,LI J J,et al.A GSTP1-mediated lactic acid signaling promotes tumorigenesis through the PPP oxidative branch[J].Cell Death Dis,2023,14(7):463.
  28. 28.
    LI G Z,WANG D,ZHAI Y,et al.Glycometabolic reprogramming-induced XRCC1 lactylation confers therapeutic resistance in ALDH1A3-overexpressing glioblastoma[J].Cell Metab,2024,36(8):1696-1710.e10.
  29. 29.
    JIN M R,WANG L,LI Y J.Effect of lactate on immune cells in tumor microenvironment and progress of related target therapy[J].Cancer Res Prev Treat,2023,50(6):634-640.
  30. 30.
    GUOX L,RENX,YANC,et al.Quantitative proteomics reveals the role of lysine lactylation in lenalidomide-resistance in multiple myeloma cells[J].ACS Chem Biol,2025,20(7):1728-1738.
  31. 31.
    LIUS Y,CHENY P,CHENJ,et al.ACACA depletion activates the cPLA2-arachidonic acid-NF-κB axis to drive inflammatory reprogramming in androgen receptor-independent prostate cancer[J].Cell Commun Signal,2025,23(1):352.
  32. 32.
    LIAOP,WANGW M,WANGW C,et al.CD8+ T cells and fatty acids orchestrate tumor ferroptosis and immunity via ACSL4[J].Cancer Cell,2022,40(4):365-378.e6.
  33. 33.
    PLATTENM,NOLLENE A A,RÖHRIGU F,et al.Tryptophan metabolism as a common therapeutic target in cancer,neurodegeneration and beyond[J].Nat Rev Drug Discov,2019,18(5):379-401.
  34. 34.
    SHAO Z F,DING P J.Research progress on the role of dyslipidemia in the pathogenesis of colorectal cancer and its related therapeutic applications[J].Shandong Med J,2020,60(32):94-97.
  35. 35.
    LIT,LUOC T,LIUZ Y,et al.Nicotinamide mononucleotide protects STAT1 from oxidative stress-induced degradation to prevent colorectal tumorigenesis[J].MedComm,2024,5(12):e70006.

더 읽기

The above content is generated by Large Model Translation. The translated content is for reference only. We do not assume any commercial or legal responsibilty for any consequences arising from the use of our website