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Cancer Lett. 2014 Jun 28;348(1-2):20-8. doi: 10.1016/j.canlet.2014.02.010. Epub 2014 Feb 15.

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

Author information

1
The State Engineering Laboratory of AIDS Vaccine, College of Life Sciences, Jilin University, Changchun, China.
2
Department of Pathophysiology College of Basic Medical Sciences, Jilin University, Changchun, China.
3
Department of Pathophysiology College of Basic Medical Sciences, Jilin University, Changchun, China. Electronic address: zhao_lj@jlu.edu.cn.
4
The State Engineering Laboratory of AIDS Vaccine, College of Life Sciences, Jilin University, Changchun, China; Department of Oncology, Wayne State University School of Medicine, Detroit, MI, USA; Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, USA. Electronic address: gey@karmanos.org.

Abstract

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.

KEYWORDS:

Drug combination; Obatoclax; Olaparib; Pancreatic cancer

PMID:
24534203
DOI:
10.1016/j.canlet.2014.02.010
[Indexed for MEDLINE]

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