GDC-0941 sensitizes breast cancer to ABT-737 in vitro and in vivo through promoting the degradation of Mcl-1

被引：34

作者：

Zheng, Lin ^{[1
]}

Yang, Wei ^{[1
]}

Zhang, Chong ^{[1
]}

Ding, Wan-jing ^{[1
]}

Zhu, Hong ^{[1
]}

Lin, Neng-ming ^{[2
]}

Wu, Hong-hai ^{[1
]}

He, Qiao-jun ^{[1
]}

Yang, Bo ^{[1
]}

机构：

[1] Zhejiang Univ, Coll Pharmaceut Sci, Inst Pharmacol & Toxicol, Hangzhou 310058, Zhejiang, Peoples R China

[2] Zhejiang Canc Hosp, Lab Clin Pharm, Hangzhou 310022, Zhejiang, Peoples R China

来源：

CANCER LETTERS | 2011年 / 309卷 / 01期

基金：

中国国家自然科学基金;

关键词：

GDC-0941; ABT-737; Synergism; Apoptosis; Mcl-1; BH3 MIMETIC ABT-737; CELL LUNG-CANCER; EFFICIENTLY INDUCES APOPTOSIS; ACUTE LYMPHOBLASTIC-LEUKEMIA; BCL-2; FAMILY-MEMBERS; INHIBITOR ABT-737; PI3K INHIBITOR; PATHWAY; RESISTANCE; EXPRESSION;

D O I：

10.1016/j.canlet.2011.05.011

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The present study showed that GDC-0941 potently sensitized breast cancer to ABT-737 in vitro and in vivo. ABT-737 exhibited limited lethality in breast cancer cells; however, when combined with GDC-0941, it displayed strong synergistic cytotoxicity and enhanced caspase-mediated apoptosis. GDC-0941 promoted proteasomal degradation of Mcl-1, of which the overexpression has been validated to confer ABT-737 resistance, thereby enhanced the anticancer efficacy of ABT-737. Furthermore, the combination of GDC-0941 and ABT-737 exerted increased anti-tumor efficacy on MDA-MB-231 xenograft models. Overall, our data described unprecedentedly the promising therapeutic potential and underlying mechanisms of combining GDC-0941 with ABT-737 in treating breast cancer. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

引用

页码：27 / 36

页数：10

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