Celastrol, a novel HSP90 inhibitor, depletes Bcr-Abl and induces apoptosis in imatinib-resistant chronic myelogenous leukemia cells harboring T315I mutation

被引：83

作者：

Lu, Zhongzheng ^{[1
]}

Jin, Yanli ^{[1
]}

Qiu, Lin ^{[2
]}

Lai, Yingrong ^{[3
]}

Pan, Jingxuan ^{[1
]}

机构：

[1] Sun Yat Sen Univ, Dept Pathophysiol, Zhongshan Sch Med, Guangzhou 510089, Guangdong, Peoples R China

[2] Harbin Inst Hematol & Oncol, Harbin, Peoples R China

[3] Sun Yat Sen Univ, Dept Pathol, Zhongshan Sch Med, Guangzhou 510089, Guangdong, Peoples R China

来源：

CANCER LETTERS | 2010年 / 290卷 / 02期

基金：

国家高技术研究发展计划(863计划);

关键词：

CML; Bcr-Abl; T315I mutation; Imatinib; Celastrol; Apoptosis; TYROSINE KINASE INHIBITOR; ONCOGENE ADDICTION; TRIPTOLIDE; TRITERPENE;

D O I：

10.1016/j.canlet.2009.09.006

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

T315I Bcr-Abl in chronic myelogenous leukemia (CML) is the most notorious point mutations to elicit acquired resistance to imatinib. In the present study, we investigated the effect of celastrol on CML cells bearing wild-type Bcr-Abl or T315I-mutant. The results revealed that celastrol potently downregulated the protein levels of Bcr-Abl, and inhibited the growth in CML cells in vitro and in nude mouse xenografts regardless of Bcr-Abl mutation status. Celastrol induced mitochondrial-dependent apoptosis. In conclusion, celastrol exhibits potent activity against CML cells bearing wild-type Bcr-Abl or -the T315I-mutant. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

引用

页码：182 / 191

页数：10

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