中文｜English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 40 Issue 10
Oct.  2024
Turn off MathJax
Article Contents
Article Navigation >  Journal of Clinical Hepatology  > 2024  >  40(10): 2049-2054

Regulatory effect of Kangxian Yiai Prescription in a rat model of precancerous lesions of liver cancer： A study based on the mTOR/HIF-1α/VEGF signaling pathway

DOI: 10.12449/JCH241019
  • 1.

    Department of Gastroenterology，Fengtai Hospital of Integrated Traditional Chinese and Western Medicine，Beijing 100072，China

  • 2.

    Department of Traditional Chinese Medicine，Beijing Xing Yuan Jin Fang Clinic of Chinese Medicine，Beijing 101300，China

  • 3.

    Institute of Liver Diseases，Beijing University of Chinese Medicine，Beijing 100700，China

Research funding:

National Natural Science Foundation of China Youth Science Fund Project (81603555);

Beijing Natural Science Foundation Youth Science Fund Project (7174319);

Beijing Fengtai Integrated Traditional Chinese and Western Medicine Hospital Natural Science Foundation (YS2022-01)

More Information
  • Corresponding author: LI Zhiguo， lizhiguo1888@163.com （ORCID： 0000-0003-3533-2542）
  • Received Date: 2024-02-04
  • Accepted Date: 2024-03-07
  • Published Date: 2024-10-25
    Abstract
  •   Objective  To investigate the effect of Kangxian Yiai Prescription （KXYA） on the mTOR/HIF-1α/VEGF signaling pathway in a rat model of precancerous lesions of liver cancer.  Methods  A total of 40 male Wistar rats were divided into normal group， model group， KXYA group， and Biejia Rangan Tablets （BJRG） group， with 10 rats in each group. The rats in the normal group were given intraperitoneal injection of normal saline at a dose of 0.4 mL/100 g， and those in the other three groups were given intraperitoneal injection of diethylnitrosamine at a dose of 50 mg/kg to establish a rat model of the precancerous lesions of liver cancer. Immunohistochemistry and Western Blot were used to measure the expression level of GST-Pi， and quantitative real-time PCR and Western Blot were used to measure the mRNA and protein expression levels of mTOR， HIF-1α， VEGF， PKM2， and GLUT1. A one-way analysis of variance or the Kruskal-Wallis H test was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups.  Results  Compared with the normal group， the model group had a significant increase in the protein expression level of GST-Pi in liver tissue （P<0.01）， and compared with the model group， the KXYA group had a significant reduction in the protein expression level of GST-Pi （P<0.05）. Compared with the normal group， the model group had significant increases in the mRNA expression levels of GLUT1 and PKM2 in liver tissue （P<0.01）， and compared with the model group， the BJRG group and the KXYA group had a significant reduction in the mRNA expression level of GLUT1 （P<0.05）. Compared with the normal group， the model group had significant increases in the protein expression levels of GLUT1 and PKM2 in liver tissue （P<0.01）. Compared with the normal group， the model group had significant increases in the mRNA expression levels of mTOR， HIF-1α， and VEGF in liver tissue （P<0.01）； compared with the model group， the BJRG group had significant reductions in the mRNA expression levels of mTOR and VEGF （P<0.05）， and the KXYA group also had significant reductions in the mRNA expression levels of mTOR and VEGF （P<0.01）. Compared with the normal group， the model group had significant increases in the protein expression levels of mTOR， HIF-1α， and VEGF in liver tissue （P<0.01）； compared with the model group， the BJRG group had a significant reduction in the protein expression level of mTOR （P<0.01）， and the KXYA group had significant reductions in the protein expression levels of mTOR， HIF-1α， and VEGF （P<0.05）； compared with the BJRG group， the KXYA group had a significantly higher protein expression level of mTOR （P<0.01）.  Conclusion  KXYA can inhibit the precancerous lesions of liver cancer by regulating the mTOR/HIF-1α/VEGF signaling pathway.

     

    • FullText(HTML)
  • loading
    • References(22)
  • [1]
    VILLANUEVA A. Hepatocellular carcinoma[J]. N Engl J Med, 2019, 380( 15): 1450- 1462. DOI: 10.1056/nejmra1713263.
    [2]
    General Office of National Health Commission. Standard for diagnosis and treatment of primary liver cancer(2022 edition)[J]. J Clin Hepatol, 2022, 38( 2): 288- 303. DOI: 10.3969/j.issn.1001-5256.2022.02.009.

    国家卫生健康委办公厅. 原发性肝癌诊疗指南(2022年版)[J]. 临床肝胆病杂志, 2022, 38( 2): 288- 303. DOI: 10.3969/j.issn.1001-5256.2022.02.009.
    [3]
    Chinese Journal of Hepatology; Liver Cancer Study Group, Chinese Society of Hepatology, Chinese Medical Association. Expert consensus on multidisciplinary diagnosis and treatment of precancerous lesions of hepatocellular carcinoma(2020 edition)[J]. J Clin Hepatol, 2020, 36( 3): 514- 518. DOI: 10.3969/j.issn.1001-5256.2020.03.007.

    《中华肝脏病杂志》编辑委员会, 中华医学会肝病学分会肝癌学组. 肝细胞癌癌前病变的诊断和治疗多学科专家共识(2020版)[J]. 临床肝胆病杂志, 2020, 36( 3): 514- 518. DOI: 10.3969/j.issn.1001-5256.2020.03.007.
    [4]
    LIU H, CHEN XT, WANG PF, et al. PRMT1-mediated PGK1 arginine methylation promotes colorectal cancer glycolysis and tumorigenesis[J]. Cell Death Dis, 2024, 15( 2): 170. DOI: 10.1038/s41419-024-06544-6.
    [5]
    LI ZG, YANG XZ, LI XK, et al. Association of hypoxic microenvironment with the development and progression of liver diseases[J]. J Clin Hepatol, 2020, 36( 8): 1891- 1895. DOI: 10.3969/j.issn.1001-5256.2020.08.047.

    李志国, 杨先照, 李小科, 等. 缺氧微环境与肝病发生发展的关系[J]. 临床肝胆病杂志, 2020, 36( 8): 1891- 1895. DOI: 10.3969/j.issn.1001-5256.2020.08.047.
    [6]
    LAPLANTE M, SABATINI DM. mTOR signaling in growth control and disease[J]. Cell, 2012, 149( 2): 274- 293. DOI: 10.1016/j.cell.2012.03.017.
    [7]
    SAXTON RA, SABATINI DM. mTOR signaling in growth, metabolism, and disease[J]. Cell, 2017, 169( 2): 361- 371. DOI: 10.1016/j.cell.2017.03.035.
    [8]
    YANG XG, LU Y, HANG JJ, et al. Lactate-modulated immunosuppression of myeloid-derived suppressor cells contributes to the radioresistance of pancreatic cancer[J]. Cancer Immunol Res, 2020, 8( 11): 1440- 1451. DOI: 10.1158/2326-6066.CIR-20-0111.
    [9]
    MUSLEH UD DIN S, STREIT SG, HUYNH BT, et al. Therapeutic targeting of hypoxia-inducible factors in cancer[J]. Int J Mol Sci, 2024, 25( 4): 2060. DOI: 10.3390/ijms25042060.
    [10]
    SCHITO L, SEMENZA GL. Hypoxia-inducible factors: Master regulators of cancer progression[J]. Trends Cancer, 2016, 2( 12): 758- 770. DOI: 10.1016/j.trecan.2016.10.016.
    [11]
    GIANNITRAPANI L, DI GAUDIO F, CERVELLO M, et al. Genetic biomarkers of sorafenib response in patients with hepatocellular carcinoma[J]. Int J Mol Sci, 2024, 25( 4): 2197. DOI: 10.3390/ijms25042197.
    [12]
    FAIVRE S, RIMASSA L, FINN RS. Molecular therapies for HCC: Looking outside the box[J]. J Hepatol, 2020, 72( 2): 342- 352. DOI: 10.1016/j.jhep.2019.09.010.
    [13]
    LIU RJ, YANG XZ, ZHANG P, et al. Efficacy observation on Kangxian yi’ai formula in rats with liver precancerous lesions[J]. World Chin Med, 2015, 10( 9): 1309- 1312. DOI: 10.3969/j.issn.1673-7202.2015.09.004.

    刘蕊洁, 杨先照, 张鹏, 等. 抗纤抑癌方干预大鼠肝癌前病变疗效观察[J]. 世界中医药, 2015, 10( 9): 1309- 1312. DOI: 10.3969/j.issn.1673-7202.2015.09.004.
    [14]
    LI Y, YE YA, LI ZG, et al. Study on the mechanism of kangxianyiai formula delay the occurrence of hepatic precancerous lesions by regulating the signal pathway of PI3K-akt[J]. Chin J Integr Tradit West Med Liver Dis, 2019, 29( 3): 240- 243, 289. DOI: 10.3969/j.issn.1005-0264.2019.03.014.

    李莹, 叶永安, 李志国, 等. 基于PI3K/Akt信号通路探讨抗纤抑癌方干预肝癌前病变的作用机制[J]. 中西医结合肝病杂志, 2019, 29( 3): 240- 243, 289. DOI: 10.3969/j.issn.1005-0264.2019.03.014.
    [15]
    LIU LP, HO RL, CHEN GG, et al. Sorafenib inhibits hypoxia-inducible factor-1α synthesis: Implications for antiangiogenic activity in hepatocellular carcinoma[J]. Clin Cancer Res, 2012, 18( 20): 5662- 5671. DOI: 10.1158/1078-0432.CCR-12-0552.
    [16]
    WANG XB, WANG N, CHEUNG F, et al. Chinese medicines for prevention and treatment of human hepatocellular carcinoma: Current progress on pharmacological actions and mechanisms[J]. J Integr Med, 2015, 13( 3): 142- 164. DOI: 10.1016/S2095-4964(15)60171-6.
    [17]
    HU B, AN HM, WANG SS, et al. Preventive and therapeutic effects of Chinese herbal compounds against hepatocellular carcinoma[J]. Molecules, 2016, 21( 2): 142. DOI: 10.3390/molecules21020142.
    [18]
    XU F, ZENG YL, LI J, et al. Mechanism of traditional Chinese medicine compound in preventing and treating hepatocellular carcinoma[J]. Chin J Exp Tradit Med Formulae, 2019, 25( 24): 196- 204. DOI: 10.13422/j.cnki.syfjx.20191921.

    徐菲, 曾杨丽, 李娟, 等. 中药复方防治肝癌作用机制研究进展[J]. 中国实验方剂学杂志, 2019, 25( 24): 196- 204. DOI: 10.13422/j.cnki.syfjx.20191921.
    [19]
    LI Y, YE YA, ZHANG LD, et al. Effects of Kangxian Yi’ai Formula on integrin α5β1/FAK signaling pathway in rats with hepatic precancerous lesions[J]. China J Tradit Chin Med Pharm, 2019, 34( 2): 759- 762.

    李莹, 叶永安, 张露丹, 等. 抗纤抑癌方对肝癌前病变大鼠整合素α5β1/FAK信号通路的影响[J]. 中华中医药杂志, 2019, 34( 2): 759- 762.
    [20]
    PAKRAVAN K, BABASHAH S, SADEGHIZADEH M, et al. MicroRNA-100 shuttled by mesenchymal stem cell-derived exosomes suppresses in vitro angiogenesis through modulating the mTOR/HIF-1α/VEGF signaling axis in breast cancer cells[J]. Cell Oncol, 2017, 40( 5): 457- 470. DOI: 10.1007/s13402-017-0335-7.
    [21]
    MIYAZAWA M, YASUDA M, FUJITA M, et al. Therapeutic strategy targeting the mTOR-HIF-1alpha-VEGF pathway in ovarian clear cell adenocarcinoma[J]. Pathol Int, 2009, 59( 1): 19- 27. DOI: 10.1111/j.1440-1827.2008.02320.x.
    [22]
    WAN XL, SHEN N, MENDOZA A, et al. CCI-779 inhibits rhabdomyosarcoma xenograft growth by an antiangiogenic mechanism linked to the targeting of mTOR/Hif-1alpha/VEGF signaling[J]. Neoplasia, 2006, 8( 5): 394- 401. DOI: 10.1593/neo.05820.
    • Relative Articles
    • Supplements(0)
    • Cited By
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(6)  / Tables(1)

    Get Citation
    PDF
    XML

    Article Metrics

    Article views (402) PDF downloads(19) Cited by()
    Proportional views
    Related
        

    The first journal specializing in hepatobiliary and pancreatic diseases in China

    Supervisor：Ministry of Education of the People's Republic of China

    Sponsor：Jilin University

    Academic Support: Chinese Society of Hepatology，Chinese Medical Association

    Address: 461 Xinjiang Road, Changchun

    Submit：0431-88782044

    Peer review：0431-88783542

    Email：lcgdb@vip.163.com

    About Journal

    Submission Guideline

    Journal Online

    Hepatobiliary College

    Guidelines

    YesterdayIP[]YesterdayPV[]TodayIP[]TodayPV[]Online[]

    Website Design © 2020 Editorial Board of Journal of Clinical Hepatology 吉ICP备10000617号-1 Supported by: Beijing Renhe Information Technology Co. Ltd  

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return