title: Bcl-xL antisense oligonucleotides chemosensitize human glioblastoma cells.
abstract: BACKGROUND
  Resistance to chemotherapy in glioblastoma has been linked to the expression of antiapoptotic Bcl-2 family members including Bcl-xL.
  
  
  METHODS
  Bcl-xL expression was specifically reduced in M059K glioblastoma cells with antisense oligonucleotides (ISIS 16009, ISIS 16967) as assessed by Western blotting. Induction of apoptosis by treatment with antisense oligonucleotides in combination with paclitaxel in cell culture was monitored by WST-1 assays and flow cytometric analysis.
  
  
  RESULTS
  Antisense oligonucleotide-mediated reduction of Bcl-xL levels led to enhanced cytotoxicity in M059K cells when compared to the use of a mismatch control oligonucleotide (p < 0.001). A decreased threshold for the induction of apoptosis led to significantly enhanced cytotoxic responses to paclitaxel treatment in WST-1 assays (p < 0.001) and flow cytometric analyses.
  
  
  CONCLUSIONS
  Combination treatment using Bcl-xL antisense oligonucleotides and paclitaxel may qualify as a promising strategy to ultimately improve the clinical outcome of glioblastoma.
authors.affiliation: Department of Clinical Pharmacology, Section of Experimental Oncology/Molecular Pharmacology, University of Vienna, Vienna, Austria.
authors.forename: Patrick
authors.initials: P
authors.lastname: Guensberg
authors.forename: Volker
authors.initials: V
authors.lastname: Wacheck
authors.forename: Trevor
authors.initials: T
authors.lastname: Lucas
authors.forename: Brett
authors.initials: B
authors.lastname: Monia
authors.forename: Hubert
authors.initials: H
authors.lastname: Pehamberger
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Eichler
authors.forename: Burkhard
authors.initials: B
authors.lastname: Jansen
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000473:pathology*; D019008:Drug Resistance, Neoplasm; D005909:Glioblastoma / Q000473:pathology*; D006801:Humans; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D017239:Paclitaxel / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D014407:Tumor Cells, Cultured; D051020:bcl-X Protein
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C494811:BCL2L1 protein, human; D016376:Oligonucleotides, Antisense; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D017239:Paclitaxel