Proteomic analysis of the resistance to Aplidin in human cancer cells

被引：37
作者：
Gonzalez-Santiago, Laura
Alfonso, Patricia
Suarez, Yajaira
Nunez, Antonio
Garcia-Fernandez, Luis F.
Alvarez, Enrique
Munoz, Alberto
Casal, J. Ignacio
机构：
[1] CNIO, Programa Bioecnol, Unidad Tecnol, E-28229 Madrid, Spain
[2] Univ Autonoma Madrid, CSIC, Inst Invest Biomed Alberto Sols, E-28029 Madrid, Spain
[3] PharmaMar SA, Madrid, Spain
来源：
JOURNAL OF PROTEOME RESEARCH | 2007年 / 6卷 / 04期
关键词：
aplidin; differential proteomics; 2D-DIGE; chemoresistance; apoptosis pathways;
D O I：
10.1021/pr060430+
中图分类号：
Q5 [生物化学];
学科分类号：
071010 ; 081704 ;
摘要：
Aplidin (plitidepsin) is an antitumoral agent that induces apoptosis via Rac1-JNK activation. A proteomic approach using 2D-DIGE technology found 52 cytosolic and 39 membrane proteins differentially expressed in wild-type and Aplidin-resistant HeLa cells, of which 39 and 27 were identified by MALDI-TOF mass spectrometry and database interrogation. A number of proteins involved in apoptosis pathways were found to be deregulated. Alterations in Rab geranylgeranyltransferase, protein disulfide isomerase (PDI), cystathionine gamma-lyase, ezrin, and cyclophilin A (CypA) were confirmed by immunoblotting. Moreover, the role of PDI and CypA in Aplidin resistance was functionally confirmed by using the inhibitor bacitracin and overexpression, respectively. These deregulated proteins are candidates to mediate, at least partially, Aplidin action and might provide a route to the cells to escape the induction of apoptosis by this drug.
引用
收藏
页码：1286 / 1294
页数：9
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