>
网站首页期刊介绍通知公告编 委 会投稿须知电子期刊广告合作联系我们
最新消息:
吡格列酮对胶质瘤细胞生长的抑制研究
作者:万政强  陈晨  伏林山  孙关 
单位:盐城市第一人民医院 神经外科, 江苏 盐城 224001
关键词:胶质瘤 吡格列酮 PPARγ β-catenin 
分类号:R739.41;R-33
出版年·卷·期(页码):2013·32·第一期(42-45)
摘要:

目的:观察PPARγ激动剂吡格列酮(pioglitazone)对胶质瘤细胞生长、迁移、凋亡等生物学行为的影响,并研究其相关分子作用机制。方法:CCK-8法、细胞划痕试验、TUNEL法检测吡格列酮对胶质瘤细胞增殖、侵袭和凋亡的影响;Western Blot法检测吡格列酮刺激后对胶质瘤细胞中相关基因表达的影响。结果:吡格列酮抑制胶质瘤细胞生长,降低细胞侵袭能力并诱导其凋亡。吡格列酮能够下调β连环蛋白(β-catenin)、MMP-2蛋白表达,上调Bad、Bax蛋白表达水平。转染β-catenin siRNA后检测发现MMP-2表达降低,Bad、Bax表达上调。结论:吡格列酮抑制胶质瘤细胞增殖和迁移,促进细胞凋亡,具有抗胶质瘤的功效。吡格列酮可能通过β-catenin介导抑制胶质瘤细胞生长。

Objective: To investigate the effects of peroxisome proliferator-activated receptor γ(PPARγ) agonist pioglitazone on the growth, invasion and apoptosis of glioma cells, and the possible mechanism. Methods: The effects of pioglitazone in different concentrations and in different action times on the growth of glioma cells were examined by CCK-8 analysis,the cell-migration by monolayer wound healing assay after pioglitazone stimulation and the apoptosis of cells under pioglitazone-treated by TUNEL method. Western Blot assay was used to evaluate the possible mechanism involve in the effect of pioglitazone. Results: Pioglitazone could effectively lead to glioma cells growth suppression, invasion reduction, and apoptosis increase. Western Blot assay showed that Bax and Bad were up-regulated and MMP-2 was down-regulated in response to pioglitazone treatment. Pioglitazone induced β-catenin repression in does-dependent and time-dependent manner. Conclusion: PPARγ agonist pioglitazone which can decrease glioma cells proliferation, migration and promote cell apoptosis displays antineoplastic effects on glioma cells. pioglitazone inhibits glioma cells growth mediated by β-catenin.

参考文献:

[1] 张建超,杨天明.磁性纳米铁治疗大鼠胶质瘤的实验研究[J].东南大学学报:医学版,2010,29(3):254-259.
[2] HOUSEKNECHT K L,COLE B M,STEELE P J.Peroxisome proliferator-activated receptor gamma (PPARgamma) and its ligands:a review[J].Domest Anim Endocrinol,2002,22(1):1-23.
[3] KOGA H,SELVENDIRAN K,SIVAKUMAR R,et al.PPARγ potentiates anticancer effects of gemcitabine on human pancreatic cancer cells[J].Int J Oncol,2012,40(3):679-685.
[4] FU H,ZHANG J,PAN J,et al.Chemoprevention of lung carcinogenesis by the combination of aerosolized budesonide and oral pioglitazone in A/J mice[J].Mol Carcinog,2011,50(12):913-921.
[5] 郭晏同,冷希圣,赵景明,等.过氧化物酶体增殖物激活受体γ配体对诱导大鼠肝癌的抑制作用[J].中华肝脏病杂志,2005,13(2):145-146.
[6] CURRAN S,MURRAY G I.Martix metalloporoteinase in tumor invasion and metastis[J].J Pathol,1999,189(3):300-308.
[7] RAO J S,STECK P A,MOHANAM S,et al.Elevated levels of M(r) 92,000 type IV collagenase in human brain tumors[J].Cancer Res,1993,53:2208-2211.
[8] FORSYTH P A,WONG H,LAING T D,et al.Gelatinase-A (MMP-2),gelatinase-B (MMP-9) and membrane type matrix metalloproteinase-1 (MT1-MMP) are involved in different aspects of the pathophysiology of malignant gliomas[J].Br J Cancer,1999,79:1828-3185.
[9] BUCHMAN J J,DURAK O,TSAI L H.ASPM regulatis Wnt signaling pathway activity in the develpoing brain[J].Genes Dev,2011,25(18):1909-1914.
[10] LIM S C,LEE M S.Significance of E-cadherin/beta-catenin complex and cyclinD1 in breast cancer[J].Oncol Rep,2002,9(5):915-928.

服务与反馈:
文章下载】【发表评论】【查看评论】【加入收藏
提示:您还未登录,请登录!点此登录
您是第 416718 位访问者


copyright ©《东南大学学报(医学版)》编辑部
联系电话:025-83272481 83272483
电子邮件:
bjb@pub.seu.edu.cn

苏ICP备09058364