Abstract
We evaluated RAD001, an inhibitor of the mammalian target of rapamycin (mTOR) in human gastric cancer cell lines and determined the molecular mechanisms. RAD001 has marked growth inhibitory activity against the SNU-1 and SNU-216 cells. It inhibited phosphorylation of mTOR and S6K, and induced G1 cell cycle arrest. Synergistic growth-inhibitory effects in combination with 5-fluorouracil (5-FU) was identified. Furthermore, RAD001 conferred sensitivity to 5-FU-resistant cell lines by downregulating thymidylate synthase (TS). In conclusion, RAD001 showed growth inhibitory activity against gastric cancer cells and acted synergistically with cytotoxic agents such as 5-FU by downregulating TS.
Copyright © 2010 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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Cell Line, Tumor
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Cell Proliferation / drug effects
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Drug Resistance, Neoplasm
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Everolimus
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Fluorouracil / pharmacology*
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G1 Phase / drug effects
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Humans
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Intracellular Signaling Peptides and Proteins / antagonists & inhibitors*
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Protein Serine-Threonine Kinases / antagonists & inhibitors*
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Sirolimus / analogs & derivatives*
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Sirolimus / pharmacology
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Stomach Neoplasms / drug therapy*
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Stomach Neoplasms / pathology
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TOR Serine-Threonine Kinases
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Thymidylate Synthase / antagonists & inhibitors*
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Thymidylate Synthase / genetics
Substances
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Intracellular Signaling Peptides and Proteins
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Everolimus
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Thymidylate Synthase
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MTOR protein, human
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Protein Serine-Threonine Kinases
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TOR Serine-Threonine Kinases
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Fluorouracil
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Sirolimus