高级搜索

华蟾素对肝癌大鼠骨髓来源树突状细胞的影响及其预防肝癌的机制

谢新梅, 何艳芬, 张洪亮

谢新梅, 何艳芬, 张洪亮. 华蟾素对肝癌大鼠骨髓来源树突状细胞的影响及其预防肝癌的机制[J]. 肿瘤防治研究, 2012, 39(10): 1183-1187. DOI: 10.3971/j.issn.1000-8578.2012.10.006
引用本文: 谢新梅, 何艳芬, 张洪亮. 华蟾素对肝癌大鼠骨髓来源树突状细胞的影响及其预防肝癌的机制[J]. 肿瘤防治研究, 2012, 39(10): 1183-1187. DOI: 10.3971/j.issn.1000-8578.2012.10.006
Xie Xinmei, He Yanfen, Zhang Hongliang. Effect of Cinobufacini on Bone Marrow Derived Dendritic Cells in Rat with Liver Cancer and Its Mechanism[J]. Cancer Research on Prevention and Treatment, 2012, 39(10): 1183-1187. DOI: 10.3971/j.issn.1000-8578.2012.10.006
Citation: Xie Xinmei, He Yanfen, Zhang Hongliang. Effect of Cinobufacini on Bone Marrow Derived Dendritic Cells in Rat with Liver Cancer and Its Mechanism[J]. Cancer Research on Prevention and Treatment, 2012, 39(10): 1183-1187. DOI: 10.3971/j.issn.1000-8578.2012.10.006

华蟾素对肝癌大鼠骨髓来源树突状细胞的影响及其预防肝癌的机制

基金项目: 乌鲁木齐市科技局资助项目(Y111310030)
详细信息
    作者简介:

    谢新梅(1963-),女,硕士,副主任医师,主要从事肿瘤的中西医结合临床治疗工作

    通讯作者:

    张洪亮,E-mail:zhanghongliang@csco.org.cn

  • 中图分类号: R735.7;R735.36+2

Effect of Cinobufacini on Bone Marrow Derived Dendritic Cells in Rat with Liver Cancer and Its Mechanism

  • 摘要: 目的 从树突状细胞(DCs)的分子细胞水平初步探讨华蟾素(CBC)预防肿瘤的作用机制。方法将20只Wistar大鼠随机分成两组,华蟾素干预组和阴性对照组各10只,0.01%二乙基亚硝胺(DEN)饮水,供两组大鼠自由饮用造成肝癌模型,共连续饮12周后再更换为正常饮水至20周,同时从第1周对干预组大鼠进行腹腔注射华蟾素(每周2次,共20周)。阴性对照组给予同等剂量的0.9%氯化钠溶液。通过核磁共振(MRI)、大体观察肝脏病变;应用重组细胞因子诱导、培养两组大鼠骨髓来源的树突状细胞(DCs),并在倒置显微镜下观察DCs的形态特点;流式细胞术检测DCs表型;ELISA法检测两组大鼠血清IL-2、IL-10浓度。结果经MRI 检测,两组大鼠肝脏 T2加权像显示均有多个小的高密度结节。CBC干预组的结节数(84.3±9.3)与阴性对照组(121.7±15.6)相比,差异具有统计学意义(P<0.05)。诱导DCs后与阴性对照组相比,倒置显微镜下CBC干预组中诱导分化形成的DCs细胞较典型。经流式细胞术检测,CBC干预组中DCs表面的CD80、CD86,MHC-Ⅱ类的阳性表达率均有明显增高。与阴性对照组比较,CBC干预组的DCs表面标志物差异均有统计学意义(P<0.05)。ELISA检测结果显示,与阴性对照组相比,CBC干预组的大鼠血清IL-2和IL-10差异均有统计学意义(P均<0.05)。结论华蟾素通过上调DCs表面标志物的表达,促进DCs的成熟度,从而抑制肝癌生长。

     

    Abstract: Objective To investigate the role of cinobufacini (CBC) in anti-tumor mechanism at the molecular level of dendritic cells (DCs). Methods Female Wistar rat model with hepatic cancer was induced by 0.01% diethylnitrosamine (DEN).Twenty Wistar rats were randomly divided into 2 groups (CBC intervention group,negative control group) after 12 weeks of DEN treatment,and received CBC intraperitoneal injection (2 times/week × 20 weeks)in intervention group or equal dosage of 0.9% saline in control group,respectively.Livers were checked at the time of 20th week by 3.0 T MRI.Using recombinant cytokine to induce and culture bone marrow derived DCs and observe the morphology characteristics under the inverted microscope.Flow cytometry was used to detect the phenotypes of DCs.ELISA was applied to test the levels of serum IL-2,IL-10. Results MRI showed that the number of tumor nodules in intervention group (84.3±9.3) was significantly less than that of in control group (121.7±15.6)(P<0.05).Compared with negative control,the morphology of DCs in CBC intervention group was more typically under the inverted microscope.Moreover,the positive expressions of phenotypes [RT 1B (MHC-Ⅱ),CD80,CD86] were increased in CBC intervention group.There were significantly differences in phenotypes between 2 groups(P<0.05).ELISA data showed that the levels of serum IL-2,IL-10 were significantly differences in CBC intervention group,compared with negative group(P<0.05). Conclusion CBC can up-regulate the expressions of DCs phenotypes,promote the mature of DCs,and enhance the secretion of Th1 cytokines to suppress the growth of liver cancer.

     

  • [1] Wang TT,Xu GX.Advancement on study of pharmacological action and clinical application of cinobufotalin[J].Guo Ji Yan Ke Za Zhi,2009,9(7):1330-3.[王婷婷,徐国兴.华蟾素的药理作用研究及临床应用进展[J].国际眼科杂志,2009,9(7):1330-3.]
    [2] Gong ZP,Chen T.Deng LR,et al.Clinical application progress of cinobufagin to cancer pain relief [J].XianDai Yao Wu Yu Lin Chuang,2010,25(4):268-71.[巩仔鹏,陈涛,邓李蓉,等.华蟾素治疗癌痛的临床应用研究进展[J].现代药物与临床,2010,25(4):268-71.]
    [3] Zhang ZY,Zhang KH,Wang CW,et al.Cytotoxocity of cinobufotalin on three digestive tract tumor cells in vitro[J].Zhong Yao Yao Li Yu Lin Chuang,1999,15(5):28-9.[张振玉,张昆和,王崇文,等.华蟾素对三种消化系肿瘤细胞杀伤机制研究[J].中药药理与临床,1999,15(5):28-9.]
    [4] Masuda Y,Kawazoe N,Nakajo S,et al.Bufalin induces apoptosis and influences the expression of apoptosis-related genes in human leukemia cells[J].Leuk Res,1995,19(8):549-56.
    [5] Sheng XS,Xu LJ.Effects of cinobufacini on apoptosis and expression of Caspase-3 in leukemia cells[J].ShiYong Zhong Liu Za Zhi,2007,22(1):32-5.[盛秀胜,徐玲娟.华蟾素诱导人红白血病细胞K562凋亡及对Caspase-3表达的影响[J].实用肿瘤杂志,2007,22(1):32-5.]
    [6] Zuo XD,Cui YA,Qin SK,et al.Effect of cinobufacini on tumor cell cycle and expression of bcl-2 protein[J].Xian Dai Zhong Xi Yi Jie Je Za Zhi,2003,12(6):567-8.[左小东,崔永安,秦叔奎,等.华蟾素对肿瘤细胞周期及bcl-2蛋白表达的影响[J].现代中西医结合杂志,2003,12(6):567-8.]
    [7] Wang NY,Li SY,Zhao W,et al.Study the effect of antiangiogenesis of ansenic trioxide in combination withcinobufacin on chick embryo chorioallantoic membrane (CAM)[J].Lin Chuang Zhong Liu Xue Za Zhi,2006,11(7):494-6.[王南瑶,李苏宜,赵伟,等.华蟾素联合三氧化二砷抑制鸡胚尿囊膜血管生成的实验研究[J].临床肿瘤学杂志,2006,11 (7):494-6.]
    [8] Reis e Sousa C.Dendritic cells as sensors of infection [J].Immunity,2001,14(5):495-8.
    [9] Banchereau J,Steinman RM.Dendritic cells and the control of immunity[J].Nature,1998,392(6673):245-52.
    [10] Ovali E,Dikmen T,Sonmez M,et al.Active immunotherapy for cancer patients using tumor lysate pulseddendritic cell vaccine:a safety study [J].J Exp Clin Cancer Res,2007,26(2):209-14.
    [11] Grayson MH,Holtzman MJ.Emerging role of dendritic cells in respiratory viral infection [J].J Mol Med(Berl),2007,85(10):1057-68.
    [12] Jung S.Good,bad and beautiful--the role of dendritic cells in autoimmunity[J].Autoimmne Rev,2004,3(1):54-60.
    [13] Radhakrishnan S,Celis E,Pease LR.B7-DC cross-linking restores antigen uptake and augments antigen-presenting cell function by matured dendritic cells [J].Proc Natl Acad Sci U S A,2005,102(32):11438-43.
    [14] Wang YF,Sun SG,He GH,et al.In vitro induction and expansion of dendritic cells from rat bone marrow andtheir characterization[J].Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi,2005,21(1):76-8.[王云甫,孙圣刚,何国厚,等.体外诱导扩增大鼠树突状细胞及其特性鉴定[J].细胞与分子免疫学杂志,2005,21(1):76-8.]
    [15] Su Y,Wang JL,Chen FQ,et al.A method to amplify and purify dendritic cells from rat bone marrow in vitro [J].Zhongguo Zu Zhi Gong Cheng Xue Yan Jiu Yu Lin Chuang Kang Fu,2007,11(50):10049-52.[苏钰,王锦玲,陈福权,等.建立大鼠骨髓源性树突状细胞体外扩增及纯化的方法[J].中国组织工程学研究与临床康复,2007,11(50):10049-52.]
    [16] Wei XL,Wang XY,Tang W.Effect of cinobufotalin on the dendritic cells derivedfrom peripheral blood of healthadults[J].Nantong Da Xue Xue Bao (Yi Xue Ban),2007,27(2):98-100.[危晓莉,汪晓莺,汤伟.华蟾素对正常人外周血来源树突状细胞的影响[J].南通大学学报(医学版),2007,27(2):98-100.]
    [17] Wei XL,Wang XY,Tang W,et al.Effect of cinobufotalin on the dendritic cells derived fromperipheral blood ofpatients with chronic hepatitis B[J].Zhong Yao Yao Li Yu Lin Chuang,2007,23(4):54-6.[危晓莉,汪晓莺,汤伟,等.华蟾素对慢性乙型肝炎患者外周血来源树突状细胞的影响[J].中药药理与临床,2007,23(4):54-6.]
    [18] Wang Y,Nv HY,Guo J,et al.Relationship between the inhibition of tumor growth and the expression of the IL-2,IFN-γ and IL-10 in spleen cells and tumor tissue of renal carcinoma in nude mice after radiotherapy[J].Di SiJun Yi Da Xue Xue Bao,2009,30(20):2122-4.[王瑶,吕海燕,郭佳,等.放射治疗荷肾癌小鼠肿瘤生长抑制与脾细胞及肿瘤组织IL-2,IFN-γ和IL-10的关系[J].第四军医大学学报,2009,30(20):2122-4.]
    [19] Abrams SI.Positive and negative consequences of Fas/Fas ligand interactions in the antitumor response[J].Front Biosci,2005,10:809-21.
    [20] Zou W.Immunosuppressive networks in the tumorenvironment and their therapeutic relevance[J].Nat RevCancer,2005,5(4):263-74.
    [21] Marotta G,Frassoldati A,Zinzani P,et al.Role of interferon-alphaadministration after 2-deoxy coformycin inthe treatment of hairy cell leukemia patients[J].Eur J Haematol,2006,77(2):109-13.
    [22] Foley JE,Mariotti J,Ryan K,et al.Th2 cell therapy of established acute graft-versus-hostdisease requiresIL-4 and IL-10 and is abrogated by IL-2 or host-type antigen-presenting cells[J].Biol Blood MarrowTransplant,2008,14(9):959-72.
    [23] Zhao XM,Chen XM,Yang ZY,et al.Effect of cinosufotalin on the level of IL-2 and LAK cell activity[J].Zhong Yao Yao Li Yu Lin Chuang,1999,15(6):33-5.[赵兴梅,陈晓明,杨祖贻,等.华蟾素注射液对人IL-2水平及LAK细胞活性的影响[J].中药药理与临床,1999,15(6):33-5.]
    [24] Liu XS,Liu KJ,Yang YJ.Effects of cinobufacini on the growth of Hela cell and IL-2 production of murinespleen lymphocytes[J].Mian Yi Xue Za Zhi,2005,21(3):132-5.[刘祥胜,刘开俊,杨业金.华蟾素对HELA细胞生长和小鼠脾淋巴细胞分泌IL-2的影响[J].免疫学杂志,2005,21(3):132-5.]
计量
  • 文章访问数:  4213
  • HTML全文浏览量:  17
  • PDF下载量:  756
  • 被引次数: 0
出版历程
  • 收稿日期:  2012-05-08
  • 修回日期:  2012-08-19
  • 刊出日期:  2012-10-24

目录

    /

    返回文章
    返回
    x 关闭 永久关闭