title: [Mechanism of temozolomide-induced anti-tumor effects on glioblastoma cells in vitro is via ROS-dependent SIRT1 signaling pathway].
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 G(2)/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.
authors.affiliation: Department of Head and Neck Surgery, Jiangsu Cancer Hospital and Research Institute, Nanjing 210009, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Jiang
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yuan
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005909:Glioblastoma / Q000473:pathology*; D006801:Humans; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D056564:Sirtuin 1 / Q000378:metabolism*; D000077204:Temozolomide
chemical_list: D018906:Antineoplastic Agents, Alkylating; D017382:Reactive Oxygen Species; D003606:Dacarbazine; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D000077204:Temozolomide