CRM1 as a new therapeutic target for non-Hodgkin lymphoma

被引：20
作者：
Han, Xiaohong
Wang, Jianfei
Shen, Yinchen
Zhang, Ningning
Wang, Shuai
Yao, Jiarui
Shi, Yuankai [1 ]
机构：
[1] Peking Union Med Coll, Canc Inst Hosp, Dept Med Oncol, Beijing 100021, Peoples R China
来源：
LEUKEMIA RESEARCH | 2015年 / 39卷 / 01期
关键词：
CRM1; inhibitor; Non-Hodgkin lymphoma; CRM1-MEDIATED NUCLEAR EXPORT; SELECTIVE INHIBITORS; DRUG-RESISTANCE; NUCLEOCYTOPLASMIC TRANSPORT; CYTOPLASMIC LOCALIZATION; SURVIVIN; PROTEINS; SIGNAL; P53; MECHANISM;
D O I：
10.1016/j.leukres.2014.10.003
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
The chromosomal region maintenance 1 (CRM1) may serve as a novel target for cancer treatment. Here, we investigated the anti non-Hodgkin lymphoma (NHL) activity of two novel CRM1 inhibitors (KPT-185 and KPT-276) in vitro and in vivo. KPT-185 displayed potent antiproliferative properties and induced cell-cycle arrest and apoptosis in several NHL cell lines and patients' tumor cells. The antitumor activity mainly consisted of inducing caspase cleavage and downregulating the expression of antiapoptotic proteins such as CRM1, nuclear factor-kappa B, and survivin. Furthermore, oral administration of KPT-276 significantly suppressed tumor growth in mice with Jeko-1 xenograft without any major toxic effects. (C) 2014 Elsevier Ltd. All rights reserved.
引用
收藏
页码：38 / 46
页数：9
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