title: Drug specific resistance to oxaliplatin is associated with apoptosis defect in a cellular model of colon carcinoma.
abstract: 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.
authors.affiliation: CNRS UMR 5094, Faculté de Pharmacie, 15 avenue Charles Flahaut, P.O. Box 14491, 34093 Montpellier, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Gourdier
authors.forename: Maguy
authors.initials: M
authors.lastname: Del Rio
authors.forename: Laure
authors.initials: L
authors.lastname: Crabbé
authors.forename: Laurent
authors.initials: L
authors.lastname: Candeil
authors.forename: Virginie
authors.initials: V
authors.lastname: Copois
authors.forename: Marc
authors.initials: M
authors.lastname: Ychou
authors.forename: Charles
authors.initials: C
authors.lastname: Auffray
authors.forename: Pierre
authors.initials: P
authors.lastname: Martineau
authors.forename: Nadir
authors.initials: N
authors.lastname: Mechti
authors.forename: Yves
authors.initials: Y
authors.lastname: Pommier
authors.forename: Bernard
authors.initials: B
authors.lastname: Pau
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology; D001483:Base Sequence; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000235:genetics; D003110:Colonic Neoplasms / Q000473:pathology*; D017931:DNA Primers; D019008:Drug Resistance, Neoplasm; D005434:Flow Cytometry; D006801:Humans; D007191:Indazoles / Q000494:pharmacology; D008954:Models, Biological; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D000077150:Oxaliplatin; D010087:Oxides / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; D017931:DNA Primers; D007191:Indazoles; D009944:Organoplatinum Compounds; D010087:Oxides; D019253:Proto-Oncogene Proteins c-bcl-2; D000077150:Oxaliplatin; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D000077237:Arsenic Trioxide; C016371:lonidamine