中国临床药理学杂志Issue(13)：1271-1275,5.DOI:10.13699/j.cnki.1001-6821.2015.13.016
替莫唑胺酯对脑胶质瘤的作用及其机制研究
Effects of temozolomide easter on glioma cells and its possible mechanisms
摘要
Abstract
Objective To investigate the contribution of temozolomide easter ( TMZ -HE ) to the proliferation and apoptosis of brain glioma LN229 cells in vitro compared with temozolomide ( TMZ) , and then test whether TMZ-HE could overcome TMZ resistance .Methods Methyl thiazolyl tetrazolium assay was used to measure the effects on the prolifer-ation of LN229 cells cultured with graded concentrations ( 62.5 , 125 , 250 , 500 , 1000 μmol・ L-1 ) of TMZ and TMZ-HE.The Annexin V and propidium iodide ( PI) assay by flow cytometer were applied to detect the apoptosis induced by TMZ and TMZ -HE.The changes of cell cycle were detected by flow cytometer .Western blot detected the expressing of Bax and Bcl -2 in LN229 after treatment with TMZ and TMZ -HE. Constructed resistant cell lines LN 229/MGMT which MGMT in LN229/MGMT was over-expressed , then the effect of TMZ-HE on re-sistant cells was detected by MTT assay .Results TMZ-HE obviously suppressed the proliferation of LN 229 glioma cells in a concentration -and time-dependent manner compared with TMZ , and the half inhibito-ry concentration ( IC50 ) value of TMZ was much higher than TMZ -HE. TMZ-HE induced more cellular apoptosis of the LN 229 cells in a con-centration -dependent manner .Furthermore , high concentration of TMZ-HE induced a distinct cell cycle arrest with accumulation of cells in S phase that is not observed for TMZ .Then TMZ -HE induced apoptosis by increasing the expression of Bax and down -regulating the level of Bcl -2.The study presented here also demonstrates that TMZ -HE is able to reverse TMZ resistance especially with high MGMT activity . Conclusion TMZ-HE inhibits more proliferation and induced more apoptosis than TMZ and TMZ -HE reversed TMZ resistance.These findings indicated that TMZ -HE may be developed as a possible therapeutic agent for the management of glioblastoma multiform .关键词
替莫唑胺酯/多形性脑胶质瘤/细胞凋亡/耐药Key words
temozolomide easter/glioma/apoptosis/resistance分类
医药卫生引用本文复制引用
郭珊珊,朱仲玲,徐辉,丁凤霞,王国成,赵敏,阎昭..替莫唑胺酯对脑胶质瘤的作用及其机制研究[J].中国临床药理学杂志,2015,(13):1271-1275,5.基金项目
“十二五”重大新药创制科技重大专项基金资助项目 （）
