[1]宫崧峰　丁建军　汪　宇　苏　娟　王新军　王茂明　李维平 高永中.抑制Hedgehog信号通路对人脑胶质瘤肿瘤干细胞体外增殖的影响[J].中国临床神经外科杂志,2015,(02):96-98.[doi:10.13798/j.issn.1009-153X.2015.02.010]
　GONG Song-feng,DING Jian-jun,WANG Yu,et al.Effect of intervention of Hedgehog signaling pathway on proliferation of human glioma stem cells in vitro[J].,2015,(02):96-98.[doi:10.13798/j.issn.1009-153X.2015.02.010]
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抑制Hedgehog信号通路对人脑胶质瘤肿瘤干细胞体外增殖的影响()
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《中国临床神经外科杂志》[ISSN:1009-153X/CN:42-1603/TN]

卷:
期数:
2015年02期
页码:
96-98
栏目:
论著
出版日期:
2015-02-28

文章信息/Info

Title:
Effect of intervention of Hedgehog signaling pathway on proliferation of human glioma stem cells in vitro
文章编号:
1009-153X（2015）02-0096-03
作者:
宫崧峰　丁建军　汪　宇　苏　娟　王新军　王茂明　李维平 高永中
518035，深圳市第二人民医院神经外科
通讯作者：丁建军，E-mail：dingdangb15@163.com
Author(s):
GONG Song-feng;  DING Jian-jun;  WANG Yu;  SU Juan;  WANG Xin-jun;  WANG Mao-ming;  LI Wei-ping;  GAO Yong-zhong.
Department of Neurosurgery, The Second People's Hospital of Shenzhen City, Shenzhen 518035, China
关键词:
胶质瘤; 肿瘤干细胞; Hedgehog信号通路; 环靶明; 细胞增殖
Keywords:
Glioma stem cell;  Hedgehog signaling pathway;  Cyclopamine;  Proliferation
分类号:
R 739.41; R 73-43
DOI:
10.13798/j.issn.1009-153X.2015.02.010
文献标志码:
A
摘要:
目的 探讨抑制Hedgehog信号通路对人脑胶质瘤肿瘤干细胞（GSCs）体外增殖的影响。方法 收集我院手术切除的胶质母细胞瘤标本，进行分离、培养和鉴定GSCs，应用环靶明抑制Hedgehog信号通路，采用免疫组化染色检测GSCs Hedgehog信号通路相关蛋白的表达，使用CCK-8试剂盒测定GSCs的增殖活性。结果 胶质母细胞瘤标本分离出来的细胞球表达CD133及Nestin；而且表达Hedgehog信号通路关键蛋白Sonic Hedgehog和Smo。环靶明对GSCs增殖的抑制率随浓度的升高显著增高（P<0.05），而且随作用时间延长显著增高（P<0.01）。结论 Hedeghog信号通路的特异性抑制剂环靶明能够显著抑制体外培养GSCs的增殖。
Abstract:
Objective To investigate the expression of Hedgehog signaling pathway in glioma stem cells (GSCs) and the effects of cyclopamine (a inhibitor of Hedgehog signaling pathway) on the proliferation of GSCs. Methods The GSCs were isolated and cultured from the glioblastomas removed by neurosurgery in our hospital. Immunohistochemical technique and fluorescence stain were used to identify GSCs and detect the expression of Hedgehog signaling pathway in GSCs. The effects of cyclopamine on the proliferation of GSCs were analysized by CCK-8. Results The suspended cell masses cultured by serum-free technique expressed CD33 and Nestin cell surface markers with strong proliferative and self-renewing ability, and was able to differentiated into glioma cells by the induction of 10% fetal bovine serum medium. Sonic Hedgehog and Smo, key proteins of Hedgehog signaling pathway, were expressed in GSCs. The Results of CCK-8 showed that the inhibitory rates of 0.5, 1 and 5 μmol/L cyclopamine to GSCs were (21.93±6.57)%, (32.03±9.13)% and (7.78±16.09)% respectively (P<0.01). The inhibitory rate of cyclopamine to GSCs 4, 12, 24, 36, 48 and 60 hours after the culture in the media contenting cyclopamine were (25.89±7.11)%, (28.00±10.00)%, (32.98±16.87)%, (35.83±17.44)% and (41.31±16.12)%, (41.58±19.72)% respectively (P<0.01). Conclusion Cyclopamine, the inhibitor of Hedgehog signaling pathway, can significantly inhibits the proliferation of GSCs in the concentration- and time-depenent fashions.

参考文献/References:

[1] Singh SK, Clarke ID, Hide T, et al. Cancer stem cells in nervous system tumors [J]. Oncogene, 2004, 23(43): 7267- 7273.
[2] Singh SK, Clarke ID, Terasaki M, et al. Identification of a cancer stem cell in human brain tumors [J]. Cancer Res, 2003, 63(18): 5821-5828.
[3] Eberhart CG. Even cancers want commitment: lineage iden- tity and medulloblastoma formation [J]. Cancer Cell, 2008, 14: 105-107.
[4] 李　斐，江普查. 神经干细胞治疗胶质瘤的研究进展 [J]. 中国临床神经外科杂志，2006，11（12）：761-764.
[5] 汪　宇，丁建军. 脑胶质瘤干细胞Hedgehog信号通路研 究进展[J]. 中国临床神经外科杂志，2014，19（12）： 763- 765.
[6] Bussolmi B, Grange C, Sapino A, et al. Endothelial cell dif- ferentiation of human breast tumour stem/progenitor cells [J]. Cell Mol Med. 2009, 13: 309-319．
[7] Shahi MH, Rey JA, Castresana JS. The sonic hedgehog- GLI1 signaling pathway in brain tumor development [J]. Expert Opin Ther Targets, 2012, 16(12): 1227-1238.
[8] 何青兰，陈　炼，秦　龙，等. Hedgehog信号通路相关基 因在人脑胶质瘤干细胞和胶质瘤组织中的表达及其意 义[J]. 中国临床神经外科杂志，2010，15（7）：423-425.

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备注/Memo

备注/Memo:
基金项目：深圳市医疗卫生类科研项目（201202047，201302237；深圳市知识创新计划（JCYJ2013401113155027，JCYJ20140414170821293）
更新日期/Last Update: 2015-02-28