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

Isabelle Gourdier , Maguy del Rio (1) , Laure Crabbe , Laurent Candeil (2) , Virginie Copois (2) , Marc Ychou (3) , Charles Auffray (4) , Pierre Martineau (2) , Nadir Mechti (2) , Yves Pommier (5) , Bernard Pau (6)

1 IRCM - U896 Inserm - UM1 - Institut de recherche en cancérologie de Montpellier
2 IRIM - Institut de Recherche en Infectiologie de Montpellier
3 Immunociblage des Tumeurs et Ingenierie des Anticorps
4 Genexpress
5 Laboratory of Molecular Pharmacology
6 UM - Université de Montpellier

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.

Domaines: Sciences du Vivant [q-bio]

Isabelle Gourdier, Maguy del Rio, Laure Crabbe, Laurent Candeil, Virginie Copois, et al.. Drug specific resistance to oxaliplatin is associated with apoptosis defect in a cellular model of colon carcinoma. FEBS Letters, 2002, 529 (2-3), pp.232-236. ⟨10.1016/s0014-5793(02)03347-1⟩. ⟨hal-02354155⟩