Additive cytotoxic effect of bortezomib in combination with anti-CD20 or anti-CD52 monoclonal antibodies on chronic lymphocytic leukemia cells

被引：29
作者：
Smolewski, Piotr
Duechler, Markus
Linke, Anna
Cebula, Barbara
Grzybowska-Izydorczyk, Olga
Shehata, Medhat
Robak, Tadeusz
机构：
[1] Med Univ Lodz, Dept Hematol, Copernicus Mem Hosp, PL-93513 Lodz, Poland
[2] AKH Vienna, Ludwig Boltzmann Inst Cytokine Res, Dept Haematol, Clin Internal Med 1, Vienna, Austria
[3] Nofer Inst Occupat Med, Dept Toxicol & Carcinogenisis, Lodz, Poland
来源：
LEUKEMIA RESEARCH | 2006年 / 30卷 / 12期
关键词：
bortezomib; B-CLL; rituximab; campath; apoptosis;
D O I：
10.1016/j.leukres.2006.03.005
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Inhibitor of proteasome, bortezomib (BOR), although highly active in vitro, showed unexpectedly low efficacy in vivo in patients with B-CLL when used alone. We studied the in vitro cytotoxic effects of BOR in combination with anti-CD20 (rituximab, RIT) or anti-CD52 (campath. CAM) monoclonal antibodies on B-CLL cells. Both BOR + RIT and BOR + CAM combinations exerted additive cytotoxicity, triggering caspase-dependent apoptosis. The treatment significantly modified expression of several apoptosis-regulating proteins, including upregulation of Bax or downregulation of Bcl-2 and Mcl-1 by BOR + RIT, as well as downregulation of Bcl-2 and XIAP by BOR + CAM. These data suggest the feasibility of concomitant use of those agents for the treatment of B-CLL patients. (c) 2006 Elsevier Ltd. All rights reserved.
引用
收藏
页码：1521 / 1529
页数：9
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