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Mechanism of temozolomide-induced anti-tumor effects on glioblastoma cells in vitro is via ROS-dependent SIRT1 signaling pathway

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Author:
No author available
Journal Title:
Chinese Journal of Oncology
Issue:
10
DOI:
10.3760/cma.j.issn.0253-3766.2012.10.004
Key Word:
替莫唑胺;神经胶质瘤;沉默信息调节因子1;活性氧;细胞增殖;细胞凋亡;Temozolomide;Glioma;Silent information regulator 1;Reactive oxygen species;Cell proliferation;Apoptosis

Abstract: Objective To investigate the new mechanism of temozolomide (TMZ) induced anti-tumor effects on glioblastoma cells in vitro.Methods Grade Ⅳ glioma cell lines SHG44 and U251 cells were treated with TMZ.MTT test was used to determine the proliferation of glioma cells.Hoechst 33342 assay was used to detect apoptosis in the tumor cells.The cell cycle progression was assessed by flow cytometry.The level of intracellular reactive oxygen species (ROS) was detected using DCFH-DA probe.real-time PCR assay and Western blotting were used to analyze the expression of SIRT1.Results Treatment with TMZ for 72 hours inhibited cell proliferation (P < 0.05) and induced apoptosis in the two cell lines in a concentration-dependent manner.TMZ at 100 μmol/L significantly resulted in G2/M cell cycle arrest (66.16%,69.65%),and triggered a robust increase in cell apoptosis [(33.4 ± 1.8) % and (26.8 ± 3.2) %].TMZ remarkably increased reactive oxygen species (ROS) production (P <0.05),indicating an overexpression of signal for SIRT1 activation.Conclusions Our findings suggest that temozolomide mediates anti-tumor effects on glioma cells in vitro via ROS-dependent SIRT1 signaling pathway,therefore,provide a theoretical evidence for a new approach to improve the treatment of glioma in future.

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