Volume 38 Issue 2
Feb.  2022
Turn off MathJax
Article Contents
LIU Tian-tian, BIAN Yong, GUAN Han-qing, LIANG Yan, GUO Wen-hui, YU Qian-hui, TANG De-cai. Study on the Inhibitory Effect of Huangqi-Ezhu-Chonglou Combination on Metastasis of Colon Cancer by Reducing Vascular Endothelial Permeability[J]. Journal of Nanjing University of traditional Chinese Medicine, 2022, 38(2): 115-121. doi: 10.14148/j.issn.1672-0482.2022.0115
Citation: LIU Tian-tian, BIAN Yong, GUAN Han-qing, LIANG Yan, GUO Wen-hui, YU Qian-hui, TANG De-cai. Study on the Inhibitory Effect of Huangqi-Ezhu-Chonglou Combination on Metastasis of Colon Cancer by Reducing Vascular Endothelial Permeability[J]. Journal of Nanjing University of traditional Chinese Medicine, 2022, 38(2): 115-121. doi: 10.14148/j.issn.1672-0482.2022.0115

Study on the Inhibitory Effect of Huangqi-Ezhu-Chonglou Combination on Metastasis of Colon Cancer by Reducing Vascular Endothelial Permeability

doi: 10.14148/j.issn.1672-0482.2022.0115
  • Received Date: 2021-10-29
    Available Online: 2022-03-01
  •   OBJECTIVE  To observe the effects of Huangqi-Ezhu-Chonglou combination (HEC) on the permeability and tight junction of human umbilical vein endothelial cells (HUVEC) and to explore the mechanism of HEC on inhibiting the hematogenous metastasis of colon cancer cells (HCT116).  METHODS  Control serum and HEC-medicated serum were prepared. The co-culture system of HUVEC-HCT116 was constructed and divided into single culture control group, co-culture model group and HEC low, medium and high dose (2.1, 4.2, 8.4 g ·kg-1) groups. In addition, HUVEC single culture control group was set up. Cell proliferation was detected by CCK-8 method; FITC-dextran method and transwell method were used to detect the permeability of HUVEC and the number of cross endothelial migration of HCT116 cells; The distribution of ZO-1 protein in HUVEC was detected by immunofluorescence; The protein expressions of RhoA, ROCK and ZO-1 were detected by Western blot.  RESULTS  The proliferation of HUVEC was inhibited after 48 h of treatment with different doses of HEC medicated serum (P < 0.01). Compared with the single culture control group, FITC-dextran penetration and the number of transendothelial migration of HCT116 in the co-culture model group significantly increased (P < 0.01), the expression of ZO-1 was down-regulated (P < 0.01), and the expressions of RhoA and ROCK were up-regulated(P < 0.01); Compared with the co-culture model group, the FITC-dextran penetration and the number of transendothelial migration of HCT116 in the HEC group significantly decreased (P < 0.05), the expression of ZO-1 protein was up-regulated (P < 0.05), and the expressions of RhoA and ROCK were down-regulated in a dose-dependent manner (P < 0.05).  CONCLUSION  HEC may regulate the expression of tight junction associated proteins ZO-1 in HUVEC by inhibiting RhoA/ROCK pathway, reduce vascular endothelial permeability, and then inhibit colon cancer hematogenous metastasis.

     

  • loading
  • [1]
    TOMITA T, KATO M, HIRATSUKA S. Regulation of vascular permeability in cancer metastasis[J]. Cancer Sci, 2021, 112(8): 2966-2974. doi: 10.1111/cas.14942
    [2]
    单云龙, 汪思亮, 祝娉婷, 等. 抑制肿瘤转移的新策略: 靶向肿瘤细胞的外渗过程[J]. 肿瘤, 2014, 34(8): 754-757. https://www.cnki.com.cn/Article/CJFDTOTAL-ZZLL201408013.htm

    SHAN YL, WANG SL, ZHU PT, et al. The new therapeutic strategy for inhibition of cancer metastasis: Targeting extravasation of cancer cells[J]. Tumor, 2014, 34(8): 754-757. https://www.cnki.com.cn/Article/CJFDTOTAL-ZZLL201408013.htm
    [3]
    CONG X, KONG W. Endothelial tight junctions and their regulatory signaling pathways in vascular homeostasis and disease[J]. Cell Signal, 2020, 66: 109485. doi: 10.1016/j.cellsig.2019.109485
    [4]
    ZIHNI C, MILLS C, MATTER K, et al. Tight junctions: From simple barriers to multifunctional molecular gates[J]. Nat Rev Mol Cell Biol, 2016, 17(9): 564-580. doi: 10.1038/nrm.2016.80
    [5]
    LIN YN, ZHANG C, XIANG PP, et al. Exosomes derived from HeLa cells break down vascular integrity by triggering endoplasmic Reticulum stress in endothelial cells[J]. J Extracell Vesicles, 2020, 9(1): 1722385. doi: 10.1080/20013078.2020.1722385
    [6]
    LI RR, QI YN, JIANG M, et al. Primary tumor-secreted VEGF induces vascular hyperpermeability in premetastatic lung via the occludin phosphorylation/ubiquitination pathway[J]. Mol Carcinog, 2019, 58(12): 2316-2326. doi: 10.1002/mc.23120
    [7]
    HARATI R, HAFEZI S, MABONDZO A, et al. Silencing miR-202-3p increases MMP-1 and promotes a brain invasive phenotype in metastatic breast cancer cells[J]. PLoS ONE, 2020, 15(10): e0239292. doi: 10.1371/journal.pone.0239292
    [8]
    张荣嘎. 芪术蚤复方对乳腺癌模型小鼠的抑制作用及机制研究[J]. 四川中医, 2018, 36(12): 53-56. https://www.cnki.com.cn/Article/CJFDTOTAL-SCZY201812020.htm

    ZHANG RG. Effect and mechanism of Qizhuzao formulation on breast cancer model[J]. J Sichuan Tradit Chin Med, 2018, 36(12): 53-56. https://www.cnki.com.cn/Article/CJFDTOTAL-SCZY201812020.htm
    [9]
    曾普华, 郜文辉, 潘敏求, 等. 益气化瘀解毒方对人肝癌裸鼠HepG2移植瘤MVD、HIF1α、VEGF/KDR表达的影响[J]. 中华中医药学刊, 2014, 32(7): 1563-1565. https://www.cnki.com.cn/Article/CJFDTOTAL-ZYHS201407010.htm

    ZENG PH, GAO WH, PAN MQ, et al. Effect of prescription of strengthening qi and clearing poison and toxin on expressions of MVD, HIF1α and VEGF/KDR from HepG2 hepatocellular carcinoma nude mice transplantation tumor[J]. Chin Arch Tradit Chin Med, 2014, 32(7): 1563-1565. https://www.cnki.com.cn/Article/CJFDTOTAL-ZYHS201407010.htm
    [10]
    彭巍, 唐建清, 龚辉, 等. 健脾消癌方治疗对大肠癌肝转移患者临床疗效、血管生成因子及QLQ-c30评分的影响[J]. 四川中医, 2021, 39(8): 76-79. https://www.cnki.com.cn/Article/CJFDTOTAL-SCZY202108024.htm

    PENG W, TANG JQ, GONG H, et al. Effect of Jianpi Xiaoai Recipe on clinical efficacy, angiogenesis factors and QLQ-c30 score for patients with liver metastases of colorectal cancer[J]. J Sichuan Tradit Chin Med, 2021, 39(8): 76-79. https://www.cnki.com.cn/Article/CJFDTOTAL-SCZY202108024.htm
    [11]
    关汉卿, 刘甜甜, 梁研, 等. 黄芪-莪术-重楼配伍对结肠癌原位移植瘤模型裸鼠肿瘤及癌旁组织中侵袭性伪足相关蛋白表达的影响[J]. 中医杂志, 2021, 62(16): 1427-1433. https://www.cnki.com.cn/Article/CJFDTOTAL-ZZYZ202116013.htm

    GUAN HQ, LIU TT, LIANG Y, et al. Effect of Huangqi-Ezhu-Chonglou combination on the expression of invadopodia-related proteins in the tumors and paracancerous tissues of nude mice with colon cancer-derived orthotopic transplant model[J]. J Tradit Chin Med, 2021, 62(16): 1427-1433. https://www.cnki.com.cn/Article/CJFDTOTAL-ZZYZ202116013.htm
    [12]
    吴幸冬, 唐德才. 黄芪配伍莪术对小鼠结肠癌细胞CT26黏附和迁移能力的影响[J]. 中医杂志, 2020, 61(13): 1176-1183. https://www.cnki.com.cn/Article/CJFDTOTAL-ZZYZ202013017.htm

    WU XD, TANG DC. Effects of compatibility of Radix astragali seu hedysa and Rhizoma curcumae on adhesion and migration ability of colon cancer cell CT26 in mice[J]. J Tradit Chin Med, 2020, 61(13): 1176-1183. https://www.cnki.com.cn/Article/CJFDTOTAL-ZZYZ202013017.htm
    [13]
    张硕, 唐德才, 谭喜莹, 等. 黄芪、莪术配伍对斑马鱼血管生成的影响[J]. 中华中医药学刊, 2020, 38(8): 179-182, 281-283. https://www.cnki.com.cn/Article/CJFDTOTAL-ZYHS202008043.htm

    ZHANG S, TANG DC, TAN XY, et al. Effect of angiogenesis by compatibility of Huangqi (Radix astragali) and ezhu (Curcuma) in zebrafsh model[J]. Chin Arch Tradit Chin Med, 2020, 38(8): 179-182, 281-283. https://www.cnki.com.cn/Article/CJFDTOTAL-ZYHS202008043.htm
    [14]
    骆殊, 尹刚, 唐德才. 黄芪甲苷与姜黄素配伍对人肝癌裸鼠原位移植瘤新生血管生成的影响[J]. 中华肿瘤防治杂志, 2016, 23(S1): 12-13. https://www.cnki.com.cn/Article/CJFDTOTAL-QLZL2016S1006.htm

    LUO S, YIN G, TANG DC. Effect of astragaloside Ⅳ combined with curcumin on angiogenesis of orthotopic transplanted human hepatocellular carcinoma in nude mice[J]. Chin J Cancer Prev Treat, 2016, 23(S1): 12-13. https://www.cnki.com.cn/Article/CJFDTOTAL-QLZL2016S1006.htm
    [15]
    AGRAWAL V, MAHARJAN S, KIM K, et al. Direct endothelial junction restoration results in significant tumor vascular normalization and metastasis inhibition in mice[J]. Oncotarget, 2014, 5(9): 2761-2777. doi: 10.18632/oncotarget.1942
    [16]
    刘珂, 邱炳勋, 邹利, 等. 黄芪及其有效成分对内皮细胞及其连接的保护作用及机制研究进展[J]. 中草药, 2016, 47(21): 3912-3917. https://www.cnki.com.cn/Article/CJFDTOTAL-ZCYO201621031.htm

    LIU K, QIU BX, ZOU L, et al. Research progress in mechanism of Astragali Radix and its active components on endothelial cells and their junction[J]. Chin Tradit Herb Drugs, 2016, 47(21): 3912-3917. https://www.cnki.com.cn/Article/CJFDTOTAL-ZCYO201621031.htm
    [17]
    许成勇, 徐冉, 王毓国, 等. 黄芪-莪术配伍对Lewis肺癌生长转移及血管生成的抑制作用及机制研究[J]. 世界中西医结合杂志, 2018, 13(5): 596-598, 602. https://www.cnki.com.cn/Article/CJFDTOTAL-SJZX201805002.htm

    XU CY, XU R, WANG YG, et al. Inhibitive effects and mechanism of the compatibility of astragali radix and curcumae rhizome on the growth, metastasis and angiogenesis in Lewis lung carcinoma[J]. World J Integr Tradit West Med, 2018, 13(5): 596-598, 602. https://www.cnki.com.cn/Article/CJFDTOTAL-SJZX201805002.htm
    [18]
    冒慧敏. 莪术成分Zedoarondiol对血管平滑肌细胞增殖和内皮细胞损伤的影响[D]. 北京: 北京中医药大学, 2017.

    MAO HM. Effects of Zedoarondiol on proliferation of vascular smooth muscle cells and injury of endothelial cells[D]. Beijing: Beijing University of Chinese Medicine, 2017.
    [19]
    赵保胜, 朱寅荻, 马勇, 等. 中药重楼研究进展[J]. 中国实验方剂学杂志, 2011, 17(11): 267-270. https://www.cnki.com.cn/Article/CJFDTOTAL-ZSFX201111083.htm

    ZHAO BS, ZHU YD, MA Y, et al. Advances in studies on paridis rhizoma[J]. Chin J Exp Tradit Med Formulae, 2011, 17(11): 267-270. https://www.cnki.com.cn/Article/CJFDTOTAL-ZSFX201111083.htm
    [20]
    胡静, 钱晓萍, 刘宝瑞, 等. 重楼醇提物抗鼠H22移植瘤血管生成的体内实验研究[J]. 现代肿瘤医学, 2010, 18(10): 1886-1889. https://www.cnki.com.cn/Article/CJFDTOTAL-SXZL201010003.htm

    HU J, QIAN XP, LIU BR, et al. Experimental study on inhibiting angiogenesis in H22 hepatoma transplantation tumor mice by alcohol extract of paridis[J]. J Mod Oncol, 2010, 18(10): 1886-1889. https://www.cnki.com.cn/Article/CJFDTOTAL-SXZL201010003.htm
    [21]
    TANG DC, ZHANG S, SHI XX, et al. Combination of astragali polysaccharide and curcumin improves the morphological structure of tumor vessels and induces tumor vascular normalization to inhibit the growth of hepatocellular carcinoma[J]. Integr Cancer Ther, 2019, 18: 1534735418824408.
    [22]
    TORNAVACA O, CHIA MH, DUFTON N, et al. ZO-1 controls endothelial adherens junctions, cell-cell tension, angiogenesis, and barrier formation[J]. J Cell Biol, 2015, 208(6): 821-838.
    [23]
    武勰, 晏馥霞. 紧密连接对肺通透性影响的研究进展[J]. 基础医学与临床, 2021, 41(2): 272-276. https://www.cnki.com.cn/Article/CJFDTOTAL-JCYL202102025.htm

    WU X, YAN FX. Research progress on the effects of tight junction on lung permeability[J]. Basic Clin Med, 2021, 41(2): 272-276. https://www.cnki.com.cn/Article/CJFDTOTAL-JCYL202102025.htm
    [24]
    FENG SR, CEN JN, HUANG YH, et al. Matrix metalloproteinase-2 and -9 secreted by leukemic cells increase the permeability of blood-brain barrier by disrupting tight junction proteins[J]. PLoS ONE, 2011, 6(8): e20599.
    [25]
    JIANG M, QIN CY, HAN MY. Primary breast cancer induces pulmonary vascular hyperpermeability and promotes metastasis via the VEGF-PKC pathway[J]. Mol Carcinog, 2016, 55(6): 1087-1095.
    [26]
    ZHANG YY, ZHAO YZ, WU Y, et al. Ophiopogon saponin C1 inhibits lung tumors by stabilizing endothelium permeability via inhibition of PKCδ[J]. Int J Biol Sci, 2020, 16(3): 396-407.
    [27]
    魏殿芳. Aspirin减少肺癌细胞释放TNF-α对体外肺癌脑转移的影响及其机制[D]. 唐山: 华北理工大学, 2020.

    WEI DF. Effect and mechanism of Aspirin reducing TNF-α release from lung cancer cells on lung cancer brain metastasis in vitro[D]. Tangshan: North China University of Science and Technology, 2020.
    [28]
    杜相宇. 以β-catenin为中心研究芪术抗癌方联合五氟尿嘧啶对CT26. WT原位移植瘤小鼠肝转移的影响[D]. 南京: 南京中医药大学, 2020.

    DU XY. Effect of Qizhu anticancer formula combined with pentafluorouracil on liver metastasis of CT26. WT orthotopic transplanted tumor mice based on β-catenin[D]. Nanjing: Nanjing University of Chinese Medicine, 2020.
    [29]
    GONZáLEZ-MARISCAL L, TAPIA R, CHAMORRO D. Crosstalk of tight junction components with signaling pathways[J]. Biochim Biophys Acta, 2008, 1778(3): 729-756.
    [30]
    赵晓云. Flt-1在小细胞肺癌细胞穿过人脑微血管内皮细胞单层中的作用及机制研究[D]. 沈阳: 中国医科大学, 2008.

    ZHAO XY. Involvement of flt-1 in small cell lung cancer cells migration through human brain microvascular endothelial cells[D]. Shenyang: China Medical University, 2008.
    [31]
    蔡倩, 郭慕真, 朱晨笛, 等. p115RhoGEF/RhoA信号通路在高糖致脑微血管内皮细胞通透性异常中的作用[J]. 营养学报, 2019, 41(2): 154-162. https://www.cnki.com.cn/Article/CJFDTOTAL-YYXX201902013.htm

    CAI Q, GUO MZ, ZHU CD, et al. Role of p115RhoGEF/RhoA signaling pathway in permeability of brain microvascular endothelial cells exposed to high glucose[J]. Acta Nutr Sin, 2019, 41(2): 154-162. https://www.cnki.com.cn/Article/CJFDTOTAL-YYXX201902013.htm
    [32]
    LI B, ZHAO WD, TAN ZM, et al. Involvement of Rho/ROCK signalling in small cell lung cancer migration through human brain microvascular endothelial cells[J]. FEBS Lett, 2006, 580(17): 4252-4260.
    [33]
    赵晓云, 李波, 曹立业, 等. 小细胞肺癌细胞诱发人脑微血管内皮细胞紧密连接的开放[J]. 解剖科学进展, 2009, 15(2): 183-187, 191. https://www.cnki.com.cn/Article/CJFDTOTAL-JPKX200902016.htm

    ZHAO XY, LI B, CAO LY, et al. Opening of tight junction of human brain microvascular endothelial cells induced by small cell lung cancer cells[J]. Prog Anat Sci, 2009, 15(2): 183-187, 191. https://www.cnki.com.cn/Article/CJFDTOTAL-JPKX200902016.htm
  • 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)

    Article Metrics

    Article views (375) PDF downloads(43) Cited by()
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return