Abstract
Intrahepatic cholangiocarcinoma (ICC) is refractory to conventional chemotherapy. We previously generated chemoresistant ICC (SCK(R)) cells and showed that AKT and ERK signaling conferred cisplatin resistance. Here, we report that epidermal growth factor receptor (EGFR) signaling and L1 cell adhesion molecule (L1CAM) conferred cisplatin resistance in SCK(R) cells in an additive fashion. Activation of EGFR connected to AKT and ERK signaling pathways may induce anti-apoptosis and promote cell proliferation, while L1CAM promoted cell proliferation by mainly activating ERK signaling. Inhibition of EGFR activation or L1ACM greatly sensitized the cells to cisplatin. EGFR and L1CAM may be important targets for ICC therapy.
Copyright © 2011 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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Antineoplastic Agents / pharmacology
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Apoptosis / drug effects
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Apoptosis / genetics
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Bile Duct Neoplasms
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Bile Ducts, Intrahepatic
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Cell Line, Tumor
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Cell Proliferation
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Cholangiocarcinoma / drug therapy*
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Cholangiocarcinoma / genetics
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Cholangiocarcinoma / metabolism*
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Cisplatin / pharmacology*
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Drug Resistance, Neoplasm
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ErbB Receptors / antagonists & inhibitors
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ErbB Receptors / metabolism*
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Extracellular Signal-Regulated MAP Kinases / metabolism
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Humans
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Liver Neoplasms / drug therapy*
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Liver Neoplasms / genetics
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Liver Neoplasms / metabolism*
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Mice
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Mice, Nude
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Neural Cell Adhesion Molecule L1 / antagonists & inhibitors
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Neural Cell Adhesion Molecule L1 / genetics
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Neural Cell Adhesion Molecule L1 / metabolism*
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Proto-Oncogene Proteins c-akt / metabolism
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Signal Transduction / drug effects
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Xenograft Model Antitumor Assays / methods
Substances
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Antineoplastic Agents
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Neural Cell Adhesion Molecule L1
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EGFR protein, human
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ErbB Receptors
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Proto-Oncogene Proteins c-akt
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Extracellular Signal-Regulated MAP Kinases
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Cisplatin