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Drug specific resistance to oxaliplatin is associated with apoptosis defect in a cellular model of colon carcinoma
Author(s) -
Gourdier Isabelle,
Del Rio Maguy,
Crabbé Laure,
Candeil Laurent,
Copois Virginie,
Ychou Marc,
Auffray Charles,
Martineau Pierre,
Mechti Nadir,
Pommier Yves,
Pau Bernard
Publication year - 2002
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(02)03347-1
Subject(s) - oxaliplatin , apoptosis , arsenic trioxide , phenotype , cancer research , clone (java method) , drug resistance , frameshift mutation , microbiology and biotechnology , mutation , biology , chemistry , colorectal cancer , cancer , genetics , gene
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.