Abstract
X-linked inhibitor of apoptosis (XIAP) is a suppressor of apoptosis that supports an increased survival and resistance to chemotherapy of human prostate cancer (PCa) cells. Effects of transient (24 h) and chronic (beyond 1 month) downregulation of XIAP in DU145 hormone refractory prostate cancer (HRPC) cells were studied. We found that transient downregulation of XIAP by siRNAs resulted in an increase of apoptosis and a decrease in Bcl-2 levels and sensitized PCa cells to cisplatin. XIAP downregulation by shRNA vector stable transfection led to upregulation of Bcl-2 protein. Our results identify the adaptability of PCa cells to chronic loss of XIAP in part through upregulation of Bcl-2 and indicate that multitargeting approach is the most effective application in the chemotherapy of human HRPC.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptation, Physiological
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Antineoplastic Agents / pharmacology
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Apoptosis / drug effects
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Apoptosis / genetics
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Blotting, Western
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Cell Line, Tumor
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Cisplatin / pharmacology
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Down-Regulation
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Drug Resistance, Neoplasm / genetics*
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Gene Expression / drug effects
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Humans
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Male
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Neoplasms, Hormone-Dependent / genetics
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Neoplasms, Hormone-Dependent / metabolism
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Oligonucleotide Array Sequence Analysis
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Prostatic Neoplasms / genetics*
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Prostatic Neoplasms / metabolism
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Proto-Oncogene Proteins c-bcl-2 / drug effects
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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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RNA Interference
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Reverse Transcriptase Polymerase Chain Reaction
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X-Linked Inhibitor of Apoptosis Protein / drug effects
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X-Linked Inhibitor of Apoptosis Protein / genetics*
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X-Linked Inhibitor of Apoptosis Protein / metabolism
Substances
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Antineoplastic Agents
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Proto-Oncogene Proteins c-bcl-2
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X-Linked Inhibitor of Apoptosis Protein
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Cisplatin