Taxol can induce phosphorylation of BCL-2 in multiple myeloma cells and potentiate dexamethasone-induced apoptosis

被引:21
作者
Kroning, R
Lichtenstein, A
机构
[1] VA W Los Angeles Hosp, Dept Med, Los Angeles, CA 90073 USA
[2] Univ Calif Los Angeles, Ctr Comprehens Canc, Los Angeles, CA 90073 USA
关键词
multiple myeloma; apoptosis; taxol; BCL-2; dexamethasone; synergistic cytotoxicity;
D O I
10.1016/S0145-2126(97)00170-7
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
We investigated the in vitro effects of paclitaxel (taxol) on multiple myeloma (MM) cells. A dose-and time-dependent induction of BCL-2 phosphorylation and apoptosis was detected in MM cell lines and two fresh clinical samples obtained from patients. A p170-overexpressing MM line and a line that did not express BCL-2 were resistant. Since phosphorylation of BCL-2 inactivates its anti-apoptotic function and could theoretically sensitize MM cells to other agents, we tested combinations of taxol and dexamethasone. Only concentrations of taxol that phosphorylated BCL-2 interacted with dexamethasone for enhanced apoptotic death. Geldanamycin, which prevented taxol-induced BCL-2 phosphorylation, also prevented the potentiated cytotoxicity. (C) 1998 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:275 / 286
页数:12
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