Combination of AZD2281 (Olaparib) and GX15-070 (Obatoclax) results in synergistic antitumor activities in preclinical models of pancreatic cancer

被引：25

作者：

Chen, Shaohua ^{[1
]}

Wang, Guan ^{[1
]}

Niu, Xiaojia ^{[1
]}

Zhao, Jianyun ^{[1
]}

Tan, Wenxi ^{[2
]}

Wang, Hebin ^{[2
]}

Zhao, Lijing ^{[2
]}

Ge, Yubin ^{[1
,3
,4
]}

机构：

[1] Jilin Univ, State Engn Lab AIDS Vaccine, Coll Life Sci, Changchun 130021, Jilin Province, Peoples R China

[2] Jilin Univ, Dept Pathophysiol, Coll Basic Med Sci, Changchun 130021, Jilin Province, Peoples R China

[3] Wayne State Univ, Sch Med, Dept Oncol, Detroit, MI USA

[4] Wayne State Univ, Sch Med, Mol Therapeut Program, Barbara Ann Karmanos Canc Inst, Detroit, MI USA

来源：

CANCER LETTERS | 2014年 / 348卷 / 1-2期

基金：

中国国家自然科学基金;

关键词：

Pancreatic cancer; Obatoclax; Olaparib; Drug combination; BCL-2; FAMILY-MEMBERS; STRAND-BREAK REPAIR; DNA-DAMAGE; HOMOLOGOUS RECOMBINATION; SENSITIVITY; INHIBITION; MECHANISMS; APOPTOSIS; CELLS; EXPRESSION;

D O I：

10.1016/j.canlet.2014.02.010

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

In this study, we explored the antitumor activities of the PARP inhibitor AZD2281 (Olaparib) and the pan-Bcl-2 inhibitor GX15-070 (Obatoclax) in six pancreatic cancer cell lines. While both agents were able to cause growth arrest and limited apoptosis, the combination of the two was able to synergistically cause growth arrest and non-apoptotic cell death. Furthermore, in an in vivo xenograft model, the combination caused substantially increased tumor necrosis compared to either treatment alone. Our results support further investigation of the combination of Bcl-2 and PARP inhibitors for the treatment of pancreatic cancer. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

引用

页码：20 / 28

页数：9

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