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.
Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antineoplastic Combined Chemotherapy Protocols / pharmacology*
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Apoptosis / drug effects
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BRCA1 Protein / genetics
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BRCA2 Protein / genetics
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Cell Survival / drug effects
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Dose-Response Relationship, Drug
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Drug Synergism
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Enzyme Inhibitors / administration & dosage
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Female
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Humans
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Indoles
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Mice, Inbred BALB C
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Mice, Nude
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Necrosis
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Pancreatic Neoplasms / drug therapy*
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Pancreatic Neoplasms / enzymology
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Pancreatic Neoplasms / genetics
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Pancreatic Neoplasms / pathology
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Phthalazines / administration & dosage
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Piperazines / administration & dosage
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Poly(ADP-ribose) Polymerase Inhibitors
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Poly(ADP-ribose) Polymerases / metabolism
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Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Pyrroles / administration & dosage
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Time Factors
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Xenograft Model Antitumor Assays
Substances
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BRCA1 Protein
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BRCA1 protein, human
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BRCA2 Protein
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BRCA2 protein, human
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Enzyme Inhibitors
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Indoles
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Phthalazines
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Piperazines
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Poly(ADP-ribose) Polymerase Inhibitors
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Proto-Oncogene Proteins c-bcl-2
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Pyrroles
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Poly(ADP-ribose) Polymerases
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obatoclax
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olaparib