Abstract
The growth potential of PC3 prostate cancer cells, sensible (PC3(par)) or resistant (PC3(res)) to the mTOR inhibitor everolimus (RAD001) was investigated. Cell growth and proliferation of PC3(res) was similar to that of PC3(par), and late apoptosis increased in PC3(par) but decreased in PC3(res) following treatment with low dosed everolimus. PC3(res) accumulated in the G2/M-phase, accompanied by cdk1, cdk2 and cyclin B elevation. Knocking down cdk1 or cyclin B distinctly blocked the growth activity of PC3(res). One reason for everolimus resistance may be up-regulation of the cdk1-cyclin B complex in prostate cancer cells, leading to enhanced progression towards G2/M.
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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Blotting, Western
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CDC2 Protein Kinase / genetics
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CDC2 Protein Kinase / metabolism*
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Cell Cycle / drug effects
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Cell Division / drug effects
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Cell Survival / drug effects
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Cyclin B / genetics
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Cyclin B / metabolism*
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Dose-Response Relationship, Drug
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Drug Resistance, Neoplasm
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Everolimus
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G2 Phase / drug effects
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Humans
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Immunosuppressive Agents / pharmacology
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Inhibitory Concentration 50
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Male
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Multiprotein Complexes / genetics
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Multiprotein Complexes / metabolism
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Prostatic Neoplasms / genetics
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Prostatic Neoplasms / metabolism
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Prostatic Neoplasms / pathology
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RNA Interference
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Sirolimus / analogs & derivatives*
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Sirolimus / pharmacology
Substances
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Cyclin B
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Immunosuppressive Agents
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Multiprotein Complexes
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Everolimus
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CDC2 Protein Kinase
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Sirolimus