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


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.


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

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