Enhanced antitumour efficacy of gimatecan in combination with Bcl-2 antisense oligonucleotide in human melanoma xenografts

Michelandrea De Cesare, Paola Perego, Sabina C. Righetti, Graziella Pratesi, Nives Carenini, Licia Rivoltini, Gabriella Zupi, Donatella Del Bufalo, Andrea Balsari, Franco Zunino

Research output: Contribution to journalArticlepeer-review

Abstract

The anti-apoptotic protein Bcl-2 has been implicated in the intrinsic resistance of melanoma to chemotherapy. The aim of this study was to investigate the effects of anti-Bcl-2 oligonucleotide oblimersen on the antitumour activity of gimatecan, a novel lipophilic camptothecin currently undergoing clinical phase II studies. Results showed a reduced sensitivity of melanoma cells to gimatecan following Bcl-2 transfection and inversely, increased cell sensitivity to gimatecan in combination with oblimersen. In in vivo studies performed in two melanoma xenografts expressing different Bcl-2 levels, the antitumour activity of oblimersen itself was modest, but the combination with gimatecan produced a significant therapeutic advantage. The combination therapy inhibited tumour growth and delayed regrowth of the two tumours tested. The enhancement of antitumour activity was observed at doses that were tolerated well. The effects of oblimersen on antitumour activity and toxicity of gimatecan were dose-dependent. The capability of oblimersen to improve the efficacy of gimatecan supports the therapeutic potential of the drug combination in the treatment of human melanoma.

Original languageEnglish
Pages (from-to)1213-1222
Number of pages10
JournalEuropean Journal of Cancer
Volume41
Issue number8
DOIs
Publication statusPublished - May 2005

Keywords

  • Bcl-2
  • Gimatecan
  • Melanoma
  • Oblimersen

ASJC Scopus subject areas

  • Cancer Research
  • Hematology
  • Oncology

Fingerprint Dive into the research topics of 'Enhanced antitumour efficacy of gimatecan in combination with Bcl-2 antisense oligonucleotide in human melanoma xenografts'. Together they form a unique fingerprint.

Cite this