Abstract
HER2-overexpressing cancer cells are resistant to cisplatin (CDDP) and doxorubicin (DXR). Here we report that SV40 T/t-common polypeptide could specifically sensitize HER2-overexpressing cancer cells to CDDP and DXR and specifically enhance CDDP- or DXR-induced apoptosis in these cells. This activity of T/t-common may be attributed to its ability to inhibit Bcl-2 and Bcl-XL and to suppress ERK activity in CDDP- or DXR-treated HER2-overexpressing cancer cells. T/t-common could enhance the antitumor activity of DXR on HER2-overexpressing ovarian tumor in NOD/SCID mice, suggesting that combination therapy using T/t-common and chemotherapeutic agents may provide a new approach for treating HER2-overexpressing cancers.
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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Animals
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Antigens, Polyomavirus Transforming / genetics
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Antigens, Polyomavirus Transforming / metabolism*
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Antineoplastic Agents / pharmacology*
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Apoptosis / drug effects
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Cisplatin / pharmacology*
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Doxorubicin / pharmacology*
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Female
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Gene Expression Regulation, Neoplastic
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Humans
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Mice
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Mice, SCID
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Ovarian Neoplasms / drug therapy
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Ovarian Neoplasms / genetics
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Ovarian Neoplasms / metabolism
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Proto-Oncogene Proteins c-bcl-2 / genetics
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Receptor, ErbB-2 / genetics
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Receptor, ErbB-2 / metabolism*
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Tumor Cells, Cultured
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Xenograft Model Antitumor Assays
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bcl-X Protein / genetics
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bcl-X Protein / metabolism
Substances
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Antigens, Polyomavirus Transforming
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Antineoplastic Agents
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BCL2L1 protein, human
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Proto-Oncogene Proteins c-bcl-2
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bcl-X Protein
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Doxorubicin
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ERBB2 protein, human
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Receptor, ErbB-2
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Cisplatin