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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