Abstract
Previously, we demonstrated that cancerous inhibitor of protein phosphatase 2A (CIP2A) mediates bortezomib-induced apoptosis in hepatocellular carcinoma cells. Herein, we report that bortezomib sensitizes solid tumor cells to radiation-induced apoptosis. Treatment with a combination of bortezomib and radiation downregulated CIP2A in a dose-dependent manner in solid tumor cells. Knockdown of CIP2A enhanced radiation-induced apoptosis in cancer cells, and ectopic expression of CIP2A in cancer cells abolished radiation-induced apoptosis. Finally, our in vivo data showed that bortezomib and radiation combination treatment decreased tumor growth significantly. Thus, bortezomib sensitized solid tumor cells to radiation through the inhibition of CIP2A.
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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Apoptosis / drug effects*
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Apoptosis / radiation effects*
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Autoantigens / metabolism
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Boronic Acids / pharmacology*
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Bortezomib
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Cell Line, Tumor
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Chemoradiotherapy
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Dose-Response Relationship, Drug
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Down-Regulation
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Humans
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Intracellular Signaling Peptides and Proteins
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Male
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Membrane Proteins / antagonists & inhibitors*
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Membrane Proteins / metabolism
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Mice
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Mice, Nude
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Neoplasms, Experimental / drug therapy*
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Neoplasms, Experimental / genetics
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Neoplasms, Experimental / metabolism
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Neoplasms, Experimental / pathology
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Neoplasms, Experimental / radiotherapy*
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Pyrazines / pharmacology*
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RNA Interference
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Radiation-Sensitizing Agents / pharmacology*
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Time Factors
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Transfection
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Tumor Burden / drug effects
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Tumor Burden / radiation effects
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Xenograft Model Antitumor Assays
Substances
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Autoantigens
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Boronic Acids
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CIP2A protein, human
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins
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Pyrazines
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Radiation-Sensitizing Agents
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Bortezomib