Abstract
Metformin is a first-line used agent for type II diabetes with few side effects. The antineoplastic effect of metformin was widely explored recently. Metformin may also be a prospective chemosensitizer or radiosensitizer in cancer treatment. In the present study, we firstly showed that metformin could effectively enhance the anti-proliferation effect of ionizing radiation (IR) on esophageal cancer (EC) cells ECa109. More potent DNA damage was observed by detection of γH2AX foci. Metformin synergistically induce apoptosis and cell cycle arrest in ECa109 cells with IR. Furthermore, the mechanisms how metformin sensitized ECa109 cells to IR may be targeting the ATM and AMPK/mTOR/HIF-1α pathways. Metformin may be a valuable agent in comprehensive treatment of EC.
Keywords:
Esophageal neoplasms; Ionizing radiation; Metformin.
Copyright © 2014 Elsevier Masson SAS. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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AMP-Activated Protein Kinases / metabolism*
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Apoptosis / drug effects
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Apoptosis / radiation effects
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Ataxia Telangiectasia Mutated Proteins / metabolism*
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Cell Cycle Checkpoints / drug effects
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Cell Cycle Checkpoints / radiation effects
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Cell Proliferation / radiation effects
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Cell Survival / drug effects
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Cell Survival / radiation effects
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Clone Cells
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DNA Damage
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DNA Repair / drug effects
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DNA Repair / radiation effects
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Enzyme Activation / drug effects
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Enzyme Activation / radiation effects
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Humans
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Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
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Metformin / pharmacology*
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Radiation, Ionizing*
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TOR Serine-Threonine Kinases
Substances
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HIF1A protein, human
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Hypoxia-Inducible Factor 1, alpha Subunit
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Metformin
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MTOR protein, human
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Ataxia Telangiectasia Mutated Proteins
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TOR Serine-Threonine Kinases
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AMP-Activated Protein Kinases