Abstract
CD133+ tumor cells are responsible for the initiation, propagation and recurrence of tumors, which raises the question of how to effectively target CD133+ tumor cells. Arsenic trioxide (As2O3) has considerable efficacy in treating solid tumors with induction of apoptosis. Here, we found that purified CD133+ gallbladder carcinoma cells are highly resistant to conventional chemotherapy. However, As2O3 effectively induces CD133+ gallbladder carcinoma cells apoptosis. Treatment with As2O3 reduces CD133 expression at transcriptional levels. Furthermore, the ectopic expression of CD133 attenuated the apoptotic effect of As2O3 on cells through activation of AKT signaling pathways. Collectively, As2O3 effectively targets CD133 in gallbladder carcinoma, providing a new mechanism of As2O3-induced cell apoptosis and a better understanding of drug resistance in gallbladder carcinoma.
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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AC133 Antigen
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Antigens, CD / biosynthesis*
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Antigens, CD / genetics
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Antineoplastic Agents / pharmacology*
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Apoptosis / drug effects
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Apoptosis / physiology
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Arsenic Trioxide
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Arsenicals / pharmacology*
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Cell Line, Tumor
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Down-Regulation / drug effects
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Drug Resistance, Neoplasm
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Gallbladder Neoplasms / drug therapy*
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Gallbladder Neoplasms / immunology
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Gallbladder Neoplasms / pathology
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Glycoproteins / biosynthesis*
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Glycoproteins / genetics
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Humans
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Neoplastic Stem Cells / drug effects*
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Neoplastic Stem Cells / immunology
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Neoplastic Stem Cells / pathology
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Oxides / pharmacology*
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Peptides / genetics
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Plasmids / genetics
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Proto-Oncogene Proteins c-akt / metabolism
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RNA, Messenger / biosynthesis
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RNA, Messenger / genetics
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Signal Transduction
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Transfection
Substances
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AC133 Antigen
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Antigens, CD
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Antineoplastic Agents
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Arsenicals
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Glycoproteins
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Oxides
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PROM1 protein, human
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Peptides
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RNA, Messenger
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Proto-Oncogene Proteins c-akt
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Arsenic Trioxide