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Synergistic cytotoxicity and molecular interaction on drug targets of sorafenib and gemcitabine in human pancreas cancer cells

Ricciardi, S.; Mey, V.; Nannizzi, S.; Pasqualetti, G.; Crea, F.; Del Tacca, M. and Danesi, R. (2010). Synergistic cytotoxicity and molecular interaction on drug targets of sorafenib and gemcitabine in human pancreas cancer cells. Chemotherapy, 56(4) pp. 303–312.

DOI (Digital Object Identifier) Link: https://doi.org/10.1159/000320031
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Abstract

Background: Current treatments have a modest impact on survival of pancreatic cancer patients and this study investigates the interaction between sorafenib and gemcitabine and the molecular pharmacodynamics of this combination.
Methods: The pancreatic cancer cells were treated with sorafenib and gemcitabine, alone or in combination. The effects of treatments were evaluated on cell proliferation, cell cycle, apoptosis, phosphorylation of Akt, c-Kit, ERK and VEGFR2, and expression of genes related to drug activity.
Results: Gemcitabine and sorafenib synergistically interacted on the inhibition of cell proliferation, and assessment of apoptosis demonstrated that drug associations increased the apoptotic index. Sorafenib reduced c-Kit, ERK and VEGFR2 activation and on the other hand, gemcitabine inhibited Akt phosphorylation. Moreover, quantitative PCR showed that sorafenib modulated the expression of genes related to gemcitabine activity, while gemcitabine induced the expression of RKIP.
Conclusion: These data demonstrate that gemcitabine and sorafenib combination displays a synergistic effect in pancreatic cancer cells.

Item Type: Journal Item
Copyright Holders: 2010 Karger
ISSN: 1421-9794
Academic Unit/School: Faculty of Science, Technology, Engineering and Mathematics (STEM) > Life, Health and Chemical Sciences
Faculty of Science, Technology, Engineering and Mathematics (STEM)
Item ID: 45842
Depositing User: Francesco Crea
Date Deposited: 24 Mar 2016 11:05
Last Modified: 07 Dec 2018 10:39
URI: http://oro.open.ac.uk/id/eprint/45842
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