Drug specific resistance to oxaliplatin is associated with apoptosis defect in a cellular model of colon carcinoma.
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.
Gourdier
Isabelle
I
CNRS UMR 5094, Faculté de Pharmacie, 15 avenue Charles Flahaut, P.O. Box 14491, 34093 Montpellier, France.
Del Rio
Maguy
M
Crabbé
Laure
L
Candeil
Laurent
L
Copois
Virginie
V
Ychou
Marc
M
Auffray
Charles
C
Martineau
Pierre
P
Mechti
Nadir
N
Pommier
Yves
Y
Pau
Bernard
B
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
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