Eupolyphaga sinensis Walker inhibits human chronic myeloid leukemia cell K562 growth by inducing G2-M phase cell cycle arrest and targeting EGFR signaling pathway and in S180 tumor-bearing mice

被引:15
作者
Dai, Bingling [1 ]
Zhan, Yingzhuan [1 ]
Qi, Junpeng [1 ]
Zhang, Yanmin [1 ]
机构
[1] Xi An Jiao Tong Univ, Sch Med, Xian 710049, Shaanxi Provinc, Peoples R China
基金
中国国家自然科学基金;
关键词
Eupolyphaga sinensis Walker; K562 cells growth; Cell cycle; EGFR signaling pathway; FACTOR RECEPTOR; LUNG-CANCER; PROTEIN-KINASE; IN-VITRO; EXPRESSION; GEFITINIB; TRANSITION; EXTRACT; BIOLOGY; AKT;
D O I
10.1016/j.etap.2014.04.010
中图分类号
X [环境科学、安全科学];
学科分类号
08 ; 0830 ;
摘要
Eupolyphaga sinensis Walker is not only used as a food to enhance immunity, but is used as a traditional Chinese medicine and is known as the "preferred drug to regulate blood flow". Previous studies have reported its potential biological activities including anticoagulation, antithrombotic, liver protective effect and antitumor effects. Our results indicated that E. sinensis Walker 70% ethanol extract exhibited anti-tumor effects on S180 (murine sarcoma cell line) cells implanted mice. It effectively inhibited K562 (human chronic myeloid leukemia cell line) cells proliferation and induced G(2)-M phase arrest accompanying through up-regulation of cyclin B1, cdc2 and down-regulation of cyclin D1, cyclin El, cdc25c and p53. In addition, it inhibited EGF secretion and EGFR kinase activity. Western blotting analysis indicated that it also inhibited the phosphorylation EGFR and activation of its downstream signaling molecules AKT and ERK. These results suggested that the antitumor mechanism of E. sinensis Walker involved altering the cell cycle and inhibiting EGFR phosphorylation in the EGFR signaling pathway. (C) 2014 Elsevier B.V. All rights reserved.
引用
收藏
页码:1177 / 1185
页数:9
相关论文
共 35 条
[1]   PROTEIN-KINASE-B (C-AKT) IN PHOSPHATIDYLINOSITOL-3-OH INASE SIGNAL-TRANSDUCTION [J].
BURGERING, BMT ;
COFFER, PJ .
NATURE, 1995, 376 (6541) :599-602
[2]   Expression and prognostic significance of cyclin B1 and cyclin A in non-small cell lung cancer [J].
Cooper, Wendy A. ;
Kohonen-Corish, Maija R. J. ;
McCaughan, Brian ;
Kennedy, Catherine ;
Sutherland, Robert L. ;
Lee, Cheok Soon .
HISTOPATHOLOGY, 2009, 55 (01) :28-36
[3]  
Feng Ying, 2009, Entomological Research, V39, P313, DOI 10.1111/j.1748-5967.2009.00236.x
[4]   Antitumor effects and chemical compositions of Eupolyphaga sinensis Walker ethanol extract [J].
Ge, Gang-feng ;
Yu, Chen-huan ;
Yu, Bing ;
Shen, Zhen-hua ;
Zhang, Dong-liang ;
Wu, Qiao-feng .
JOURNAL OF ETHNOPHARMACOLOGY, 2012, 141 (01) :178-182
[5]   Molecular predictors of outcome with gefitinib in a phase III placebo-controlled study in advanced non-small-cell lung cancer [J].
Hirsch, Fred R. ;
Varella-Garcia, Marileila ;
Bunn, Paul A., Jr. ;
Franklin, Wilbur A. ;
Dziadziuszko, Rafal ;
Thatcher, Nick ;
Chang, Alex ;
Parikh, Purvish ;
Rodrigues Pereira, Jose ;
Ciuleanu, Tudor ;
von Pawel, Joachim ;
Watkins, Claire ;
Flannery, Angela ;
Ellison, Gillian ;
Donald, Emma ;
Knight, Lucy ;
Parums, Dinah ;
Botwood, Nicholas ;
Holloway, Brian .
JOURNAL OF CLINICAL ONCOLOGY, 2006, 24 (31) :5034-5042
[6]   Maturation promoting factor, cyclin and the control of M-phase [J].
Hunt, T. .
CURRENT OPINION IN CELL BIOLOGY, 1989, 1 (02) :268-274
[7]   Epidermal growth factor receptor: mechanisms of activation and signalling [J].
Jorissen, RN ;
Walker, F ;
Pouliot, N ;
Garrett, TPJ ;
Ward, CW ;
Burgess, AW .
EXPERIMENTAL CELL RESEARCH, 2003, 284 (01) :31-53
[8]   Epidermal growth factor receptor biology (IMC-C225) [J].
Kim, ES ;
Khuri, FR ;
Herbst, RS .
CURRENT OPINION IN ONCOLOGY, 2001, 13 (06) :506-513
[9]  
Lew D J, 1992, Trends Cell Biol, V2, P77, DOI 10.1016/0962-8924(92)90076-Y
[10]   Significant cytotoxic activity in vitro of the EGFR tyrosine kinase inhibitor gefitinib in acute myeloblastic leukaemia [J].
Lindhagen, Elin ;
Eriksson, Anna ;
Wickstrom, Malin ;
Danielsson, Katarina ;
Grundmark, Birgitta ;
Henriksson, Roger ;
Nygren, Peter ;
Aleskog, Anna ;
Larsson, Rolf ;
Hoglund, Martin .
EUROPEAN JOURNAL OF HAEMATOLOGY, 2008, 81 (05) :344-353