Effect of bcl-2 antisense oligodeoxynucleotides on drug sensitivity of leukemic cells

Hematol J. 2003;4(3):187-97. doi: 10.1038/sj.thj.6200245.

Abstract

Introduction: We investigated the effect of two antisense oligodeoxynucleotides, previously selected with the help of computer-aided RNA structure prediction, on drug sensitivity, bcl-2 expression and apoptosis of leukemia cells. The drugs tested were etoposide (VP-16), cytarabine (Ara-C), daunorubicin (DNR) and arsenic trioxide (As(2)O(3)).

Materials and methods: The experimental assays were performed with cultures, IC(50) of leukemic cells to drugs, immunochemistry and flow cytometry.

Results: The results showed that the two antisense oligodeoxynucleotides significantly reduced IC(50) levels for VP-16, Ara-c, DNA and As(2)O(3), inhibited bcl-2 gene expression and induced apoptosis of leukemic cells.

Conclusions: Computational prediction of antisense efficacy is faster than other methods and more cost-efficient. This could hasten the development of sequences for both research and clinical applications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Apoptosis / drug effects
  • Drug Evaluation, Preclinical
  • Drug Interactions
  • Drug Resistance, Neoplasm*
  • Flow Cytometry
  • HL-60 Cells
  • Humans
  • Inhibitory Concentration 50
  • K562 Cells
  • Leukemia / drug therapy*
  • Leukemia / pathology
  • Oligodeoxyribonucleotides, Antisense / pharmacology*
  • Proto-Oncogene Proteins c-bcl-2 / analysis
  • Proto-Oncogene Proteins c-bcl-2 / drug effects
  • Proto-Oncogene Proteins c-bcl-2 / genetics*

Substances

  • Oligodeoxyribonucleotides, Antisense
  • Proto-Oncogene Proteins c-bcl-2