高级搜索

紫铆因抑制膀胱癌细胞增殖的体内外研究

张丽瑞, 陈 葳, 李 琛, 李 旭

张丽瑞, 陈 葳, 李 琛, 李 旭. 紫铆因抑制膀胱癌细胞增殖的体内外研究[J]. 肿瘤防治研究, 2014, 41(07): 714-718. DOI: 10.3971/j.issn.1000-8578.2014.07.006
引用本文: 张丽瑞, 陈 葳, 李 琛, 李 旭. 紫铆因抑制膀胱癌细胞增殖的体内外研究[J]. 肿瘤防治研究, 2014, 41(07): 714-718. DOI: 10.3971/j.issn.1000-8578.2014.07.006
ZHANG Lirui, CHEN Wei, LI Chen, LI Xu. Butein Inhibits Cell Proliferation of Bladder Cancer in vitro and in vivo[J]. Cancer Research on Prevention and Treatment, 2014, 41(07): 714-718. DOI: 10.3971/j.issn.1000-8578.2014.07.006
Citation: ZHANG Lirui, CHEN Wei, LI Chen, LI Xu. Butein Inhibits Cell Proliferation of Bladder Cancer in vitro and in vivo[J]. Cancer Research on Prevention and Treatment, 2014, 41(07): 714-718. DOI: 10.3971/j.issn.1000-8578.2014.07.006

紫铆因抑制膀胱癌细胞增殖的体内外研究

基金项目: 陕西省科技攻关项目资助课题(2012SF2-03);西安市科技计划项目资助课题(SF1204(5b))
详细信息
    作者简介:

    张丽瑞(1975-),女,博士,主治医师,主要从事肿瘤增殖侵袭分子机制的研究

    通信作者:

    李旭,E-mail:lixu56@mail.xjtu.edu.cn

  • 中图分类号: R73-36;R737.14

Butein Inhibits Cell Proliferation of Bladder Cancer in vitro and in vivo

  • 摘要: 目的 观察紫铆因对膀胱移行细胞癌细胞BLS增殖的影响以及对膀胱癌裸鼠移植瘤生长的影响。方法 不同浓度紫铆因处理细胞,四甲基偶氮唑蓝比色实验(MTT)及平板克隆形成实验观察细胞增殖能力,流式细胞仪分析细胞周期,蛋白印迹检测核转录因子κB (NF-κB)p65核内表达及细胞外信号调节激酶1/2(ERK1/2)的磷酸化程度,并检测NF-κB下游靶基因细胞周期素D1(Cyclin D1)及环氧合酶-2(COX2)的表达。建立膀胱癌裸鼠皮下移植瘤,采用腹腔注射的给药途径,测量移植瘤的体积和重量。结果 紫铆因抑制了膀胱癌细胞增殖并诱导G2/M期细胞周期阻滞。紫铆因处理后NF-κB p65的核内表达及ERK1/2的磷酸化程度下降(P<0.05),Cyclin D1及COX2基因表达下调(P<0.05),体内实验发现紫铆因治疗组较对照组皮下移植瘤的生长明显受抑制(P<0.05)。结论 紫铆因具有抗膀胱癌细胞增殖作用,可能与其抑制ERK及NF-κB信号激活有关。

     

    Abstract: Objective To investigate the effects of Butein on proliferation of BLS cells in human bladder transitional cell carcinoma(BTCC) in vitro and on transplantation tumor growth of bladder carcinoma in nude mice. Methods BLS cells were treated with Butein at various concentrations. Cell proliferation was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assay and clone formation assay, and cell cycle was detected by flow cytometry. Western blot was applied to measure phosphorylation of extra cellular signal regulated kinase(ERK1/2), nuclear transcription factor kappa B (NF-κB) p65 expression, Cyclin D1 and COX2 expressions in downstream target genes of NF-κB. Transplanted tumors of bladder cancer in nude mice were constructed. Administration route was intraperitoneal injection. Volume and weight of transplanted tumors were measured. Results Butein inhibited cell growth and induced G2/M cell cycle arrest in bladder cancer cells. Phosphorylation of ERK1/2 and NF-κB p65 intranuclear expression were reduced(P<0.05); Protein expressions of Cyclin D1 and COX2 were decreased(P<0.05); Growth of transplant subcutaneous tumor in treatment group was obviously inhibited(P<0.05). Conclusion Butein has anti-proliferation effect on human bladder cancer cells in vitro and in vivo possibly through suppressing ERK and NF-κB activation.

     

  • [1] Yang YC, Li X, Chen W. Differential expression of immuneassociated genes in two subcloned cell lines from a same human bladder cancer[J]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi, 2006, 22 (5): 625-7.[杨玉琮,李旭,陈葳.免疫相关基因在同一膀胱癌 亚克隆细胞株中的差异表达[J]. 细胞与分子免疫学杂志, 2006, 22 (5): 625-7.]
    [2] Lau GT, Huang H, Lin SM, et al. Butein downregulates phorbol 12 -myristate 13-acetate- induced COX-2 transcriptional activity in cancerous and non-cancerous breast cells[J]. Eur J Pharmacol, 20 10, 648(1-3): 24-30.
    [3] Chua AW, Hay HS, Rajendran P, et al. Butein downregulates chemokine receptor CXCR4 expression and function through suppression of NF-κB activation in breast and pancreatic tumor cells[J]. Biochem Pharmacol, 2010, 80(10): 1553-62.
    [4] Rajendran P, Ong TH, Chen L, et al. Suppression of signal transducer and activator of transcription 3 activation by butein inhibits growth of human hepatocellular carcinoma in vivo[J]. Clin Cancer Res, 2011, 17(6): 1425-39.
    [5] Johnson GL, Lapadat R. Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases[J]. Science, 2002, 298(5600): 1911-2.
    [6] Yang EB, Zhang K, Cheng LY, et al. Butein, a specific protein tyrosine kinase inhibitor[J]. Biochem Biophys Res Commun, 19 98, 245(2): 435-8.
    [7] Yang LH, Ho YJ, Lin JF, et al. Butein inhibits the proliferation of breast cancer cells through generation of reactive oxygen species and modulation of ERK and p38 activities[J]. Mol Med Rep, 20 12, 6(5): 1126-32.
    [8] Nakano H, Shindo M, Sakon S, et al. Differential regulation of lkappaB kinase alpha and beta by two upstream kinases, NFkappaB- inducing kinase and mitogen-activated protein kinase/ ERK kinase kinase-1[J]. Proc Natl Acad Sci U S A, 1998, 95(7): 35 37-42.
    [9] Mang YX, Li M. Progress in NF-κB Targeting Drugs for the Prevention and Treatment of Tumor[J]. Zhong Liu Fang Zhi Yan Jiu, 2006, 33(6): 465-7. [马艳霞, 李敏. NF-κB与肿瘤防治药物 研究进展[J]. 肿瘤防治研究, 2006, 33(6): 465-7.]
    [10] Pandey MK, Sandur SK, Sung B, et al. Butein, atetrahydroxychalcone, inhibits nuclear factor (NF)-kappa B and NF-kappaB-regulated gene expression through direct inhibition of lkappaBalpha kinase beta on cysteine-179 residue[J]. J Biol Chem, 2007, 282(24): 17 340-50.
    [11] Dahlman JM, Wang J, Bakkar N, et al. The RelA/p65 subunit of NF-kappaB specifically regulates cyclin D1 protein stability: implications for cell cycle withdrawal and skeletal myogenesis[J]. J Cell Biochem, 2009, 106(1): 42-51.
    [12] Wang S, Liu Z, Wang L, et al. NF-kappaB signaling pathway, inflammation and colorectal cancer[J]. Cell Mol Immunol, 2009, 6( 5): 327-34.
计量
  • 文章访问数:  1731
  • HTML全文浏览量:  416
  • PDF下载量:  653
  • 被引次数: 0
出版历程
  • 刊出日期:  2014-07-24

目录

    /

    返回文章
    返回
    x 关闭 永久关闭