Abstract
We evaluated the effects of sunitinib monotherapy and in combination with cisplatin in human gastric cancer cell lines. Sunitinib showed antiproliferative effect in gastric cancer cells line with high PDGFRA expression. Knockdown of PDGFRA showed that sunitinib sensitivity was correlated with the basal expression of PDGFRA. Synergistic growth inhibitory activity in combination with cisplatin was identified. We further explored how sunitinib potentiated the activity of cisplatin. We found that sunitinib treatment resulted in the down-regulation of ERCC1 expression via the modulation of PDGFRA expression in gastric cancer cells. The effect was verified via SNU484 xenograft model. Our data support the rationale of clinical trial using sunitinib in combination of cisplatin in gastric cancer.
Copyright © 2012 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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Antineoplastic Combined Chemotherapy Protocols / pharmacology*
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use
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Blotting, Western
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Cisplatin / pharmacology*
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Cisplatin / therapeutic use
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DNA Mutational Analysis
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DNA-Binding Proteins / drug effects
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DNA-Binding Proteins / metabolism*
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Down-Regulation
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Drug Synergism
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Endonucleases / drug effects
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Endonucleases / metabolism*
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Enzyme-Linked Immunosorbent Assay
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Gene Expression
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Humans
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Immunohistochemistry
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Indoles / pharmacology*
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Indoles / therapeutic use
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Pyrroles / pharmacology*
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Pyrroles / therapeutic use
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Receptor, Platelet-Derived Growth Factor alpha / metabolism*
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Stomach Neoplasms / drug therapy
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Stomach Neoplasms / metabolism*
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Stomach Neoplasms / pathology
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Sunitinib
Substances
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DNA-Binding Proteins
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Indoles
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Pyrroles
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Receptor, Platelet-Derived Growth Factor alpha
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ERCC1 protein, human
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Endonucleases
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Cisplatin
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Sunitinib