• 中国精品科技期刊
  • 中国高校百佳科技期刊
  • 中国中文核心期刊
  • 中国科学引文数据库核心期刊
Advanced Search
ZHU Yaqi, YAN Fang, DI Bin, YAN Jia, LI Jiachang, LI Yunman. Inhibiting effect of emodin on adriamycin-resistance of K562/ADM cell line[J]. Journal of China Pharmaceutical University, 2014, 45(4): 462-468. DOI: 10.11665/j.issn.1000-5048.20140414
Citation: ZHU Yaqi, YAN Fang, DI Bin, YAN Jia, LI Jiachang, LI Yunman. Inhibiting effect of emodin on adriamycin-resistance of K562/ADM cell line[J]. Journal of China Pharmaceutical University, 2014, 45(4): 462-468. DOI: 10.11665/j.issn.1000-5048.20140414

Inhibiting effect of emodin on adriamycin-resistance of K562/ADM cell line

More Information
  • The aim of the study was to evaluate and explore the inhibition effect of emodin on the adriamycin-resistance in K562/ADM cell line. In this study, verapamil and adriamycin were used as positive drug and tool drug, respectively. Cell viability was measured by MTT. The effect of emodin combined with adriamycin on cell cycle and apoptosis was determined by flowcytometry. The protein expression of P-gp, Bcr-Abl and STAT5 was analyzed by Western blot. Emodin inducing conformational change of P-gp with UIC2 antibody was detected by FCM. The results showed that emodin dramatically enhanced the cytotoxic effect of adriamycin in a concentration-dependent manner. Emodin promoted cell cycle arrest in G2/M phase and adriamycin-induced apoptosis. It down-regulated the protein expression levels of P-gp, Bcr-Abl and STAT5. The results of the UIC2 binding experiment showed that emodin may not be the substrate of P-gp. It could effectively inhibit adriamycin-resistance in vivo. The mechanism of emodin inhibiting drug-resistance of K562/ADM may be related to the decrease of P-gp, Bcr-Abl and STAT5 protein expression, instead of competitive inhibition of P-gp.
  • [1]
    Kimura S,Ando T,Kojima K,et al.Ever-advancing chronic myeloid leukemia treatment[J].Int J Clin Oncol,2014,19(1):3-9.
    [2]
    Arana-Trejo RM, Ruiz SE, Ignacio-Ibarra G, et al. BCR/ABL p210,p190 and p230 fusion genes in 250 Mexican patients with chronic myeloid leukaemia(CML)[J].Clin Lab Haematol,2002,24(3):145-150.
    [3]
    O′Hare T, Eide CA, Deininger MW. Bcr-Abl kinase domain mutations,drug resistance,and the road to a cure for chronic myeloid leukemia[J].Blood,2007,110(7):2 242-2 249.
    [4]
    Dulucq S,Bouchet S,Turcq B,et al.Multidrug resistance gene(MDR1)polymorphisms are associated with major molecular responses to standard-dose imatinib in chronic myeloid leukemia[J].Blood,2008,112(5):2 024-2 027.
    [5]
    Baccarani M,Deininger MW,Rosti G,et al.European LeukemiaNet recommendations for the management of chronic myeloid leukemia:2013[J].Blood,2013,122(6):872-884.
    [6]
    Srinivas G,Babykutty S,Sathiadevan PP,et al.Molecular mechanism of emodin action:transition from laxative ingredient to an antitumor agent[J].Med Res Rev,2007,27(5):591-608.
    [7]
    Guo J,Li W,Shi H,et al.Synergistic effects of curcumin with emodin against the proliferation and invasion of breast cancer cells through upregulation of miR-34a[J].Mol Cell Biochem,2013,382(1/2):103-111.
    [8]
    Huang XZ,Wang J,Huang C,et al.Emodin enhances cytotoxicity of chemotherapeutic drugs in prostate cancer cells:the mechanisms involve ROS-mediated suppression of multidrug resistance and hypoxia inducible factor-1[J].Cancer Biol Ther,2008,7(3):468-475.
    [9]
    Nicoletti I,Miglirati G,Pagliacci MC,et al.A rapid and simple method for measuring thymocyte apoptosis by propodium iodide staining and flow cytometry[J].J Immunol Methods,1991,139(2):271-279.
    [10]
    Wang XF,Ge JB,Wang KQ,et al.Effects of emodin on fluorescence analysis[J].Fudan Univ J Med Sci(复旦大学学报 医学版),2006,33(2):262-265.
    [11]
    Turhan AG.STAT5 as a CML target:STATinib therapies[J].Blood,2011,117(12):3 252-3 253.
    [12]
    Berger A,Hoelbl-Kovacic A,Bourgeais J,et al.PAK-dependent STAT5 serine phosphorylation is required for BCR-ABL-induced leukemogenesis[J].Leukemia,2013.doi: 10.1038/leu.2013.351.
    [13]
    Nelson EA,Walker SR,Weisberg E,et al.The STAT5 inhibitor pimozide decreases survival of chronic myelogenous leukemia cells resistant to kinase inhibitors[J].Blood,2011,117(12):3 421-3 429.
    [14]
    Nagy H,Goda K,Arceci R,et al.P-Glycoprotein conformational changes detected by antibody competition[J].Eur J Biochem,2001,268(8):2 416-2 420.
    [15]
    Maki N,Hafkemeyer P,Dey S.Allosteric modulation of human P- glycoprotein.Inhibition of transport by preventing substrate translocation and dissociation[J].J Biol Chem,2003,278(20):18 132-18 139.
    [16]
    Katalin椠????楲潥汮??框攬浚??楬??自?????扴??????戾???????????????????? of P- glycoprotein by simultaneous treatment with a distinct class of modulators and the UIC2 monoclonal antibody[J].J Pharm Exp Ther,2007,320(1):81-88.
    [17]
    Zhang Y,Wang P,Wang JR,et al.Study of intestinal absorption of emodin in one-way intestinal perfusion rat model[J].Tradit Chin Drug Res Clin Pharmacol(中药新药与临床药理),2012,23(3):286-290.
    [18]
    Wang JR.Research on intestinal absorption mechanism of rhubarb anthraquinone through intestinal perfusion(在体单向灌流法评价大黄蒽醌肠吸收机制研究)[D].Chengdu:Chengdu University of Traditional Chinese Medicine,2011.
    [19]
    Zhen ZH.Effects of emodin on chronic myelogenous leukemia K562 cells and drug-resistant K562 cells(大黄素对慢性粒细胞白血病K562细胞株及其耐药细胞株的作用及机制研究)[D].Fujian:Fujian Medical University,2009.
    [20]
    Siddik ZH,Mehta K.Drug Resistance in Cancer Cells[M].New York:Springer US,2009:1-22.
    [21]
    Chang G.Multidrug resistance ABC transporters[J].FEBS Lett,2003,555(1):102-109.
    [22]
    Yang CZ,Luan FJ,Xiong DS,et al.Multidrug resistance in leukemic cell line K562/A02 induced by doxorubicin[J].Acta Pharm Sin,1995,16(4):333-337.
    [23]
    Choi RJ,Ngoc TM,Bae K,et al.Anti-inflammatory properties of anthraquinones and their relationship with the regulation of P-glycoprotein function and expression[J].Eur J Pharm Sci,2013,48(1/2):272-281.
    [24]
    Zhang W,Chen H,Liu DL,et al.Emodin sensitizes the gemcitabine-resistant cell line Bxpc-3/Gem to gemcitabine via downregulation of NF-κB and its regulated targets[J].Int J Oncol,2013,42(4):1 189-1 196.
    [25]
    Hoelbl A,Schuster C,Kovacic B,et al.Stat5 is indispensable for the maintenance of bcr/abl-positive leukemia[J].EMBO Mol Med,2010,2(3):98-110.
    [26]
    Ritchie TK, Kwon H, Atkins WM. Conformational analysis of human ATP-binding cassette transporter ABCB1 in lipid nanodiscs and inhibition by the antibodies MRK16 and UIC2[J].<
  • Related Articles

    [1]ZHU Song, JIANG Jing, LIU Yang, ZOU Wenyu, HU Pengwei, LU Yuting, SONG Min, HANG Taijun. Structural identification of the related substances of lorazepam tablets by LC-MS[J]. Journal of China Pharmaceutical University, 2021, 52(5): 555-565. DOI: 10.11665/j.issn.1000-5048.20210507
    [2]LIANG Fangmei, NI Yueling, WANG Lu, HANG Taijun, SONG Min. Structural identification of the related substances of fusidic acid by LC-MS[J]. Journal of China Pharmaceutical University, 2018, 49(3): 322-332. DOI: 10.11665/j.issn.1000-5048.20180311
    [3]YIN Xiaoya, WANG Cheng, MING Guojun, HANG Taijun. Identification of the related substances in pioglitazone hydrochloride by hyphenated LC-MS techniques[J]. Journal of China Pharmaceutical University, 2017, 48(6): 701-710. DOI: 10.11665/j.issn.1000-5048.20170611
    [4]XU Guijun, LI Zhijun, WANG Qi, TAN Jiejun, SHI Guoshan, QI Wei, LI Di, WANG Youpeng. Isolation and identification of anti-inflammatory constituents from Houttuynia cordata[J]. Journal of China Pharmaceutical University, 2016, 47(3): 294-298. DOI: 10.11665/j.issn.1000-5048.20160308
    [5]CHEN Wenhua, ZOU Limin, ZHANG Fei, ZHANG Liandi, LIAO Mingyi, DING Li. Identification of the related substances in bendamustine hydrochloride[J]. Journal of China Pharmaceutical University, 2015, 46(3): 333-338. DOI: 10.11665/j.issn.1000-5048.20150312
    [6]ZHOU Yongmei, SHI Xianming, MA Lei, ZHANG Sifang. Isolation and identification of Withaphysalins from Physalis minima[J]. Journal of China Pharmaceutical University, 2015, 46(1): 62-65. DOI: 10.11665/j.issn.1000-5048.20150107
    [7]RAO Ya-kun, DING Li, YU Yong. Structural identification of two major impurities in sodium levofolinate[J]. Journal of China Pharmaceutical University, 2012, 43(4): 350-354.
    [8]WANG Ying, YIN Hong-ping, CHEN Tao, WANG Min. Preliminary structural identification and protection on renal cell injury of acidic polysaccharide from Cordyceps sinensis[J]. Journal of China Pharmaceutical University, 2009, 40(6): 559-564.
    [9]Structure Studies of N-(4-chlorobenzyl)-2,3-methylenedio-xyl-9-acetoxyl-10-methoxy-7,8,13,13a-tetrahydro-8H-dibenzo-quinolizine chloride[J]. Journal of China Pharmaceutical University, 2002, (1): 72-74.
    [10]IDENTIFICATION OF SYNTHETIC BY-PRODUCT N-(4-CHLOROBENZOYL)-DICYCLOHEXANYLUREA BY FOURIER TRANSFORM MASS SPECTROMETRY[J]. Journal of China Pharmaceutical University, 1989, (6): 367-369.

Catalog

    Article views (791) PDF downloads (1298) Cited by()

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return