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

被引：69

作者：

Gourdier, I

Del Rio, M

Crabbé, L

Candeil, L

Copois, V

Ychou, M

Auffray, C

Martineau, P

Mechti, N

Pommier, Y

Pau, B

机构：

[1] Fac Pharm Montpellier, CNRS, UMR 5094, F-34093 Montpellier, France

[2] Ctr Reg Lutte Contre Canc Val Aurelle, Serv Oncol Digest, F-34298 Montpellier, France

[3] CNRS FRE 2376, F-94801 Villejuif, France

[4] Natl Canc Inst, Mol Pharmacol Lab, Bethesda, MD 20890 USA

来源：

FEBS LETTERS | 2002年 / 529卷 / 2-3期

关键词：

oxaliplatin; drug resistance; apoptosis; Bax; colorectal cancer;

D O I：

10.1016/S0014-5793(02)03347-1

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

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. (C) 2002 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.

引用

页码：232 / 236

页数：5

共 24 条

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