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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2011-2-9
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pubmed:abstractText |
Insulin-like growth factor 1 (IGF-1) inhibits 5-fluorouracil (5-Fu)-induced apoptosis in esophageal carcinoma cells; however, the mechanisms for IGF-1-induced 5-Fu chemoresistance remain unknown. In the human esophageal carcinoma cell line, CE48T/VGH, we show that IGF-1 up-regulated survivin expression at the post-transcriptional level and this up-regulation is mediated by both the PI3-K/Akt and casein kinase 2 signaling pathways. We then examine whether IGF-1-induced 5-Fu chemoresistance is mediated through up-regulation of survivin. Ectopic expression of survivin inhibits 5-Fu-induced apoptosis; furthermore, the abolition of survivin expression sensitizes cells to 5-Fu treatment and prevents the anti-apoptotic function of IGF-1 in esophageal carcinoma cell lines. We also found that ectopic expression of survivin or treatment with IGF-1 inhibits the release of Smac/DIABLO and caspases activation after 5-Fu treatment. Our results strongly suggest that IGF-1 inhibits 5-Fu induced apoptosis through increasing survivin levels, which prevents Smac/DIABLO release and blocks the activation of caspases. Therefore, up-regulation of IGF-1 and survivin would seem to be responsible for 5-Fu chemoresistance in esophageal cancer patients and these factors may be the valuable predictors of 5-Fu chemoresistance in esophageal carcinoma.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antimetabolites, Antineoplastic,
http://linkedlifedata.com/resource/pubmed/chemical/BIRC5 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Casein Kinase II,
http://linkedlifedata.com/resource/pubmed/chemical/DIABLO protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Fluorouracil,
http://linkedlifedata.com/resource/pubmed/chemical/Inhibitor of Apoptosis Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin-Like Growth Factor I,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Mitochondrial Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Oncogene Protein v-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1573-675X
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
16
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
174-83
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pubmed:meshHeading |
pubmed-meshheading:21082354-Antimetabolites, Antineoplastic,
pubmed-meshheading:21082354-Apoptosis,
pubmed-meshheading:21082354-Blotting, Western,
pubmed-meshheading:21082354-Casein Kinase II,
pubmed-meshheading:21082354-Cell Line, Tumor,
pubmed-meshheading:21082354-Drug Resistance, Neoplasm,
pubmed-meshheading:21082354-Esophageal Neoplasms,
pubmed-meshheading:21082354-Fluorouracil,
pubmed-meshheading:21082354-Humans,
pubmed-meshheading:21082354-Inhibitor of Apoptosis Proteins,
pubmed-meshheading:21082354-Insulin-Like Growth Factor I,
pubmed-meshheading:21082354-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:21082354-Mitochondria,
pubmed-meshheading:21082354-Mitochondrial Proteins,
pubmed-meshheading:21082354-Oncogene Protein v-akt,
pubmed-meshheading:21082354-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:21082354-Polymerase Chain Reaction,
pubmed-meshheading:21082354-Signal Transduction
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pubmed:year |
2011
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pubmed:articleTitle |
Insulin-like growth factor 1 mediates 5-fluorouracil chemoresistance in esophageal carcinoma cells through increasing survivin stability.
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pubmed:affiliation |
Institute of Public Health, National Yang-Ming University, No.155, Sec.2, Linong Street, Taipei 11221, Taiwan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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