Drug specific resistance to oxaliplatin is associated with apoptosis defect in a cellular model of colon carcinoma

FEBS Lett. 2002 Oct 9;529(2-3):232-6. doi: 10.1016/s0014-5793(02)03347-1.


To investigate acquired resistance to oxaliplatin, we selected two resistant clones from the HCT116 cell line. We found that the resistant phenotype was associated with resistance to oxaliplatin-induced apoptosis as demonstrated by FACS analysis and by Western blotting of caspase 3 activation. In addition, the resistant phenotype showed a concomitant resistance to lonidamine and arsenic trioxide which are inducers of mitochondrial apoptosis. Furthermore, a complete loss of Bax expression due to a frameshift mutation was observed in the most resistant clone. Taken together, these findings suggest that altered mitochondrial-mediated apoptosis could play a role in oxaliplatin resistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis*
  • Arsenic Trioxide
  • Arsenicals / pharmacology
  • Base Sequence
  • Blotting, Western
  • Caspase 3
  • Caspases / genetics
  • Colonic Neoplasms / pathology*
  • DNA Primers
  • Drug Resistance, Neoplasm
  • Flow Cytometry
  • Humans
  • Indazoles / pharmacology
  • Models, Biological*
  • Organoplatinum Compounds / pharmacology*
  • Oxaliplatin
  • Oxides / pharmacology
  • Proto-Oncogene Proteins c-bcl-2 / genetics


  • Antineoplastic Agents
  • Arsenicals
  • DNA Primers
  • Indazoles
  • Organoplatinum Compounds
  • Oxides
  • Proto-Oncogene Proteins c-bcl-2
  • Oxaliplatin
  • CASP3 protein, human
  • Caspase 3
  • Caspases
  • Arsenic Trioxide
  • lonidamine