Abstract
Chemoresistance of ovarian cancer can be overcome by co-administration of retinoids, albeit clinical proof of this hypothesis is pending. Moreover, growth factor/c-erbB signaling is crucial for ovarian tumor growth/chemosensitivity. Retinoids and c-erbB modulators therefore represent promising drugs for ovarian cancer. We demonstrate that c-erbB-1 (RG-14620, AG1517) and c-erbB-2 selective tyrphostins (AG825, AG879), and all-trans and 9-cis retinoic acid inhibit ovarian cancer cell proliferation (HOC-7, OVCAR-3). Unlike retinoids, AG1517 and AG879 induce apoptosis. The antiproliferative activity of AG1517 is enhanced by all-trans retinoic acid suggesting that c-erbB and retinoid pathways interact. Thus, these agents cooperate during ovarian cancer cell growth inhibition.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenocarcinoma / enzymology
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Adenocarcinoma / pathology*
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Apoptosis / drug effects
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Benzothiazoles
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Cell Division / drug effects
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Drug Resistance, Neoplasm
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Drug Synergism
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ErbB Receptors / antagonists & inhibitors
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Female
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Humans
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Neoplasm Proteins / antagonists & inhibitors
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Ovarian Neoplasms / enzymology
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Ovarian Neoplasms / pathology*
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Quinazolines / pharmacology*
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Receptor, ErbB-2 / antagonists & inhibitors
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Tretinoin / pharmacology*
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Tumor Cells, Cultured / cytology
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Tumor Cells, Cultured / drug effects
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Tumor Cells, Cultured / enzymology
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Tyrphostins / pharmacology*
Substances
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AG 1517
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AG-879
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Benzothiazoles
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Neoplasm Proteins
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Quinazolines
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Tyrphostins
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tyrphostin AG825
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RG 14620
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Tretinoin
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ErbB Receptors
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Receptor, ErbB-2