Gamma secretase inhibitor-I exerted cytotoxic effects on malignant glionm cell lines by inducing cell cycle arrest and apoptosis
10.3760/cma.j.issn.1671-8925.2010.06.008
- VernacularTitle:I型γ-分泌酶抑制剂对恶性胶质瘤细胞株增殖及凋亡的影响
- Author:
Yong-Bin YE
1
;
Jun LIN
;
Jia-Jia ZHAO
;
Xing-Mei ZHANG
;
Shen-Qiu LUO
Author Information
1. 南方医科大学
- Keywords:
Gamma-secretase inhibitor;
Glioma;
Cell cycle;
Apoptosis
- From:
Chinese Journal of Neuromedicine
2010;9(6):571-575
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the role of gamma secretase inhibitor-I (GSI-I) in cell proliferation and apoptosis of human glioma cell lines U87 and U251.Methods RT-PCR and fluorescent quantitative RT-PCR (qRT-PCR) were employed to evaluate the expressions of Notch receptors and their target gene Hes-I in both U87 and U251 cells treated by GSI-I,respectively.Then,MTT assay was used to examine the effects of GSI-I on cell proliferation of the 2 glioma cells.Meanwhile,flow cytometry technique was also employed to detect the cell cycle changes and apoptosis induced by GSI-I treatment.Results The activity of Notch pathway was inhibited by GSI-I treatment through down-regulating the expression of Notch receptors target gene Hes-I in both U87 and U251 cells.Treatment with 2.5μmol/L GSI-I or above concentrations could significantly induce the cell cycle arrest of U87 and U251 cells and these effects were positively concentration-dependent.Flow cytometry technique showed that GSI-I inhibited the cell proliferation by inducing the cell cycle arrest of U87 cells at GI phase and inducing the apoptosis of U251 cells.Conclusion GSI-I can dramatically inhibit the cell proliferation and induce the apoptosis of U87 and U251 cells,providing a reliable evidence for clinical glioma treatment.
