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Front Pharmacol. 2018 Feb 19;9:84. doi: 10.3389/fphar.2018.00084. eCollection 2018.

Proteomic Analysis of Combined Gemcitabine and Birinapant in Pancreatic Cancer Cells.

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1
Department of Pharmaceutical Sciences, University at Buffalo, The State University of New York, Buffalo, NY, United States.
2
Department of Biochemistry, University at Buffalo, The State University of New York, Buffalo, NY, United States.

Abstract

Pancreatic cancer is characterized by mutated signaling pathways and a high incidence of drug resistance. Comprehensive, large-scale proteomic analysis can provide a system-wide view of signaling networks, assist in understanding drug mechanisms of action and interactions, and serve as a useful tool for pancreatic cancer research. In this study, liquid chromatography-mass spectrometry-based proteomic analysis was applied to characterize the combination of gemcitabine and birinapant in pancreatic cancer cells, which was shown previously to be synergistic. A total of 4069 drug-responsive proteins were identified and quantified in a time-series proteome analysis. This rich dataset provides broad views and accurate quantification of signaling pathways. Pathways relating to DNA damage response regulations, DNA repair, anti-apoptosis, pro-migration/invasion were implicated as underlying mechanisms for gemcitabine resistance and for the beneficial effects of the drug combination. Promising drug targets were identified for future investigation. This study also provides a database for systems mathematical modeling to relate drug effects and interactions in various signaling pathways in pancreatic cancer cells.

KEYWORDS:

birinapant; drug resistance; drug targets; gemcitabine; pancreatic cancer cells; proteomics; signaling pathways

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