Abstract
The kinetics and effect of hyper activated IGF-1R signaling is not well investigated during acquirement of platinum and taxol resistance in ovarian cancer cells. Herein we reported an upregulated IGF-1R expression in early stages of cisplatin paclitaxel and cisplatin-taxol resistance. Picropodophyllin, an IGF-1R inhibitor, alone and in combination with cisplatin, paclitaxel or both at lowest possible doses could reverse the resistance at early stages. Upregulated IGF-1R was also found in primary tumors of ovarian cancer patients after three to four cycles of platinum-taxol treatment. These findings indicate that a combination of cytotoxic agents and IGF-1R inhibitor is more effective at early stages of chemoresistant ovarian cancer.
Keywords:
Chemoresistance; IGF-1R signaling; Ovarian 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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Antineoplastic Combined Chemotherapy Protocols / pharmacology*
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Carcinoma, Ovarian Epithelial
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Cell Line, Tumor
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Cisplatin / administration & dosage
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Cisplatin / pharmacology*
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Down-Regulation
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Drug Resistance, Neoplasm
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Drug Synergism
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Female
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Humans
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Molecular Targeted Therapy
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Neoplasm Staging
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Neoplasms, Glandular and Epithelial / drug therapy*
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Neoplasms, Glandular and Epithelial / metabolism
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Neoplasms, Glandular and Epithelial / pathology
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Ovarian Neoplasms / drug therapy*
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Ovarian Neoplasms / metabolism
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Ovarian Neoplasms / pathology
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Paclitaxel / administration & dosage
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Paclitaxel / pharmacology*
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Podophyllotoxin / administration & dosage
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Podophyllotoxin / analogs & derivatives*
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Podophyllotoxin / pharmacology
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Proteasome Endopeptidase Complex / metabolism
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Receptor, IGF Type 1 / antagonists & inhibitors*
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Receptor, IGF Type 1 / biosynthesis
Substances
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picropodophyllin
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Receptor, IGF Type 1
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Proteasome Endopeptidase Complex
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Podophyllotoxin
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Paclitaxel
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Cisplatin