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

FEBS Letters

Crabbé, Laure⁴  Gourdier, Isabelle⁴  Ychou, Marc¹  Martineau, Pierre⁴  Copois, Virginie⁴  Del Rio, Maguy⁴  Auffray, Charles³  Candeil, Laurent⁴  Pommier, Yves²  Mechti, Nadir⁴  Pau, Bernard⁴ 

[1] Service d'Oncologie Digestive, Centre Régional de Lutte Contre le Cancer Val d'Aurelle, 35 rue de la Croix Verte, 34298 Montpellier, France;Laboratory of Molecular Pharmacology, National Cancer Institute, Blg. 37, Room 4E28, 37 Convent Drive MSC 4255, Bethesda, MD 20890-4255, USA;Genexpress-CNRS FRE 2376, 7, rue Guy Moquet, P.O. Box 8, 94801 Villejuif, France;CNRS UMR 5094, Faculté de Pharmacie, 15, avenue Charles Flahaut, P.O. Box 14491, 34093 Montpellier, France

关键词: Oxaliplatin;    Drug resistance;    Apoptosis;    Bax;    Colorectal cancer;    5-FU;    5-fluorouracil;    FACS;    fluorescence-activated cell sorter;    FITC;    fluorescein isothiocyanate;    MMR;    mismatch repair;   

DOI  :  10.1016/S0014-5793(02)03347-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown