• 中国中文核心期刊
  • 中国科学引文数据库核心期刊
  • 中国科技核心期刊
  • 中国高校百佳科技期刊
高级检索

千层纸素诱导人慢性粒细胞白血病K562的凋亡作用

王玉, 赵丽, 缪瀚驰, 李志裕, 郭青龙

王玉, 赵丽, 缪瀚驰, 李志裕, 郭青龙. 千层纸素诱导人慢性粒细胞白血病K562的凋亡作用[J]. 中国药科大学学报, 2014, 45(2): 232-236. DOI: 10.11665/j.issn.1000-5048.20140218
引用本文: 王玉, 赵丽, 缪瀚驰, 李志裕, 郭青龙. 千层纸素诱导人慢性粒细胞白血病K562的凋亡作用[J]. 中国药科大学学报, 2014, 45(2): 232-236. DOI: 10.11665/j.issn.1000-5048.20140218
WANG Yu, ZHAO Li, MIAO Hanchi, LI Zhiyu, GUO Qinglong. Apoptosis induction of oroxylin A in human chronic myelogenous leukemia cell line K562[J]. Journal of China Pharmaceutical University, 2014, 45(2): 232-236. DOI: 10.11665/j.issn.1000-5048.20140218
Citation: WANG Yu, ZHAO Li, MIAO Hanchi, LI Zhiyu, GUO Qinglong. Apoptosis induction of oroxylin A in human chronic myelogenous leukemia cell line K562[J]. Journal of China Pharmaceutical University, 2014, 45(2): 232-236. DOI: 10.11665/j.issn.1000-5048.20140218

千层纸素诱导人慢性粒细胞白血病K562的凋亡作用

基金项目: 国家“重大新药创制”科技重大专项资助项目(No.2012ZX09103101-050);国家自然科学基金资助项目(No.81373448,No.81173086)

Apoptosis induction of oroxylin A in human chronic myelogenous leukemia cell line K562

  • 摘要: 探讨千层纸素对人慢性粒细胞白血病细胞K562的凋亡诱导作用及其可能机制。采用MTT法检测细胞存活率;电镜下观察细胞超微结构的改变;DAPI染色观察细胞凋亡;流式细胞仪检测细胞凋亡率;Western blot法分析凋亡相关蛋白caspase 9、survivin及ERK1/2的表达变化情况。结果表明千层纸素呈浓度依赖地抑制K562细胞的增殖作用,诱导K562细胞发生凋亡,上调 K562细胞中cleaved-caspase 9蛋白,下调survivin、pro-caspase 9及p-ERK1/2蛋白的表达水平。千层纸素可诱导K562凋亡,这可能与下调survivin蛋白表达,激活caspase 9蛋白,抑制ERK信号通路有关。
    Abstract: To investigate the apoptotic effect of oroxylin A on human chronic myelogenous leukemia cell line K562 and its potential mechanism. K562 cells were treated with oroxylin A. MTT assay was performed to assess growth inhibition effect of oroxylin A on K562 cells. The morphological change of cells were observed under electronic microscope. DAPI staining and flow cytometry were employed to observe the apoptosis rate of K562 cells. Changes in the expression of caspase 9, survivin and ERK1/2 were analyzed by Western blotting. Results showed that oroxylin A inhibited the growth of K562 in a time and dose-dependent manner. Oroxylin A induced cell apoptosis was characterized by appearance of numerous engorged vacuoles, reduction of microvilli on cell surface, condensation of chromatin and emergence of apoptotic body. Besides, oroxylin A dose-dependently induced K562 cell apoptosis, up-regulated the expression of cleaved-caspase 9 and down-regulated expression of survivin, pro-caspase 9 and p-ERK1/2 proteins. In conclusion, all these results showed that oroxylin A can induce apoptosis of K562 cells, which might be related to the down-regulation of survivin expression, activation of caspase 9 and inhibition of ERK signaling pathway.
  • [1] Wong RS, Cheong SK. Leukaemic stem cells: drug resistance,metastasis and therapeutic implications[J].Malaysian J Pathol,2012, 34(2):77-88.
    [2] Junia V.Melo,Timothy P.Hughes,et al.Chronic myeloid leukemia[J].Hematology,2003.
    [3] Kusio-Kobialka M,Podszywalow-Bartnicka P,Peidis P,et al.The PERK-eIF2α phosphorylation arm is a pro-survival pathway of BCR-ABL signaling and confers resistance to imatinib treatment in chronic myeloid leukemia cells[J].Cell Cycle,2012,11(21):4 069-4 078.
    [4] Gao Y, Lu N, Ling Y, et al. Oroxylin A inhibits angiogenesis through blocking vascular endothelial growth factor-induced KDR/Flk-1 phosphorylation[J].J Cancer Res Clin Oncol,2009,136(5):667-675.
    [5] Li HN,Nie FF,Liu W,et al.Apoptosis induction of oroxylin A in human cervical cancer HeLa cell line in vitro and in vivo[J].Toxicology,2009,257(1/2):80-85.
    [6] Zhu B,Zhao L,Zhu L,et al.Oroxylin A reverses CAM-DR of HepG2 cells by suppressing Integrinβ1 and its related pathway[J].Toxicol Appl Pharmacol,2012,259(3):387-394.
    [7] Yang HY,Zhao L,Yang Z,et al.Oroxylin a reverses multi-drug resistance of human hepatoma BEL7402/5-FU cells via downregulation of P-glycoprotein expression by inhibiting NF-κB signaling pathway[J].Molecular Carcinogenesis,2012,51(2):185-195.
    [8] Sun Y, Lu N, Ling Y, et al. Oroxylin A suppresses invasion through down-regulating the expression of matrix metalloproteinase-2/9 in MDA-MB-435 human breast cancer cells[J].Eur J Pharmacol,2009,603(1/2/3):22-28.
    [9] Zhu L,Zhao L,Wang H,et al.Oroxylin A reverses P-glycoprotein-mediated multidrug resistance of MCF7/ADR cells by G2/M arrest[J].Toxicol Lett,2013,219(2):107-115.
    [10] Yao J,Hu R,Sun J,et al.Oroxylin A prevents inflammation-related tumor through down-regulation of inflammatory gene expression by inhibiting NF-κB signaling[J].Mol Carcinog,2014,53(2):145-58.doi: 10.1002/mc.21958.
    [11] Farias-de-Oliveira DA,Villa-Verde DM,Nunes Panzenhagen PH,et al.Caspase-8 and caspase-9 mediate thymocyte apoptosis in trypanosoma cruzi acutely infected mice[J].J Leukoc Biol,2013,93(2):227-234.
    [12] Cheung CH,Huang CC,Tsai FY,et al.Survivin-biology and potential as a therapeutic target in oncology[J].Onco Targets Ther,2013,6:1 453-1 462.
    [13] Gough DJ,Koetz L,Levy DE.The MEK-ERK pathway is necessary for serine phosphorylation of mitochondrial STAT3 and Ras-mediated transformation[J].PLoS ONE,2013,8(11):e83395.
计量
  • 文章访问数: 
  • HTML全文浏览量:  0
  • PDF下载量: 
  • 被引次数: 0
出版历程
  • 刊出日期:  2014-04-24

目录

    /

    返回文章
    返回
    x 关闭 永久关闭