Down-regulation of Bcl-2 and Bcl-xL expression with bispecific antisense treatment in glioblastoma cell lines induce cell death

J Neurochem. 2003 Jan;84(2):273-81. doi: 10.1046/j.1471-4159.2003.01522.x.


The functions of the antiapoptotic proteins Bcl-2 and Bcl-xL were examined in glioblastoma cells. Expression of both Bcl-2 and Bcl-xL were found to be elevated in protein lysates from seven early passage cell lines derived from human glioblastoma tumors compared with non-neoplastic glial cells. Down-regulation of both bcl-2 and bcl-xL expression in glioblastoma cell lines U87 and NS008 with bcl-2/bcl-xL bispecific antisense oligonucleotide resulted in spontaneous cell death. The mechanism of cell death was partially caspase-dependent. Executioner caspase 6 and caspase 7, but not caspase 3, were involved in apoptosis induced by bcl-2/bcl-xL antisense treatment. Interestingly, western blots failed to demonstrate expression of caspase 3 in two of the seven glioblastoma cell lines examined. The data support the hypothesis that Bcl-2 and Bcl-xL are important in preventing cell death in glioblastoma cells. It also suggests that there are functional pathways capable of successful completion of caspase-dependent cell death in gliomas. These findings support a potential role of bcl-2/bcl-xL bispecifc antisense oligonucleotide therapy as a treatment strategy to enhance caspase-dependent cell death in patients with glioblastoma.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Caspases / metabolism
  • Cell Death / drug effects
  • Down-Regulation / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Glial Fibrillary Acidic Protein / biosynthesis
  • Glioblastoma / drug therapy*
  • Glioblastoma / metabolism*
  • Glioblastoma / pathology
  • Humans
  • Oligonucleotides, Antisense / genetics
  • Oligonucleotides, Antisense / pharmacology*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Substrate Specificity / genetics
  • Transfection
  • Tumor Cells, Cultured / drug effects
  • bcl-X Protein


  • BCL2L1 protein, human
  • Glial Fibrillary Acidic Protein
  • Oligonucleotides, Antisense
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-X Protein
  • Caspases