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rdf:type |
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lifeskim:mentions |
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pubmed:dateCreated |
2009-9-2
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pubmed:abstractText |
A recent study reported on the efficacy of the EGFR inhibitor on locally advanced vulvar cancer. The aim of this study was to evaluate the effect of an EGFR tyrosine kinase inhibitor (AG1478) alone and in combination with cisplatin on vulvar cancer cells (A431 and SW962). We detected overexpression of EGFR in A431 cells and low expression in SW962 cells. We found that the growth inhibitory effect of AG1478 was dependent upon the expression level of EGFR. The combined treatment of AG1478 with cisplatin failed to exert any synergistic or additive effect in either cell line. In the EGFR signaling pathway, AG1478 decreased the phosphorylation of extracellular signal-regulated kinase (ERK) and protein kinase B (Akt) in parallel with decreased activity of EGFR in A431 cells, while no changes in ERK and Akt were observed in SW962 cells. The combination of AG1478 with cisplatin completely inhibited the phosphorylation of ERK and Akt in A431 cells but not in SW962 cells. Cisplatin alone and its combination with AG1478 increased the phosphorylation of p38 and c-Jun N-terminal kinase (JNK) in both cell lines. In summary, AG1478 inhibited the growth activity of vulvar cancer cells, depending upon the expression level of EGFR, by inhibiting the activities of EGFR, Akt, and ERK. Given the absence of synergistic effects from the combination of AG1478 with cisplatin, combination therapy should be considered cautiously.
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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/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Cisplatin,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/JNK Mitogen-Activated Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrphostins,
http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/tyrphostin AG 1478
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1749-6632
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
1171
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
642-8
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:19723115-Antineoplastic Agents,
pubmed-meshheading:19723115-Blotting, Western,
pubmed-meshheading:19723115-Cell Line, Tumor,
pubmed-meshheading:19723115-Cell Proliferation,
pubmed-meshheading:19723115-Cell Survival,
pubmed-meshheading:19723115-Cisplatin,
pubmed-meshheading:19723115-Dose-Response Relationship, Drug,
pubmed-meshheading:19723115-Enzyme Inhibitors,
pubmed-meshheading:19723115-Female,
pubmed-meshheading:19723115-Humans,
pubmed-meshheading:19723115-JNK Mitogen-Activated Protein Kinases,
pubmed-meshheading:19723115-Mitogen-Activated Protein Kinase 1,
pubmed-meshheading:19723115-Mitogen-Activated Protein Kinase 3,
pubmed-meshheading:19723115-Phosphorylation,
pubmed-meshheading:19723115-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:19723115-Receptor, Epidermal Growth Factor,
pubmed-meshheading:19723115-Tyrphostins,
pubmed-meshheading:19723115-Vulvar Neoplasms,
pubmed-meshheading:19723115-p38 Mitogen-Activated Protein Kinases
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pubmed:year |
2009
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pubmed:articleTitle |
Effect of epidermal growth factor receptor inhibitor alone and in combination with cisplatin on growth of vulvar cancer cells.
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pubmed:affiliation |
Cancer Research Institute, World Class University, Seoul National University, Seoul, Korea.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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