Source:http://linkedlifedata.com/resource/pubmed/id/16361577
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
24 Pt 1
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| pubmed:dateCreated |
2005-12-19
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| pubmed:abstractText |
Tumor cells that have acquired resistance to gefitinib through continuous drug administration may complicate future treatment. To investigate the mechanisms of acquired resistance, we established PC-9/ZD2001, a non-small-cell lung cancer cell line resistant to gefitinib, by continuous exposure of the parental cell line PC-9 to gefitinib. After 6 months of culture in gefitinib-free conditions, PC-9/ZD2001 cells reacquired sensitivity to gefitinib and were established as a revertant cell line, PC-9/ZD2001R. PC-9/ZD2001 cells showed collateral sensitivity to several anticancer drugs (vinorelbine, paclitaxel, camptothecin, and 5-fluorouracil) and to tumor necrosis factor alpha (TNF-alpha). Compared with PC-9 cells, PC-9/ZD2001 cells were 67-fold more sensitive to TNF-alpha and PC-9/ZD2001R cells were 1.3-fold more sensitive. Therefore, collateral sensitivity to TNF-alpha was correlated with gefitinib resistance. PC-9/ZD2001 cells expressed a lower level of epidermal growth factor receptor (EGFR) than did PC-9 cells; this down-regulation was partially reversed in PC-9/ZD2001R cells. TNF-alpha-induced autophosphorylation of EGFR (cross-talk signaling) was detected in all three cell lines. However, TNF-alpha-induced Akt phosphorylation and IkappaB degradation were observed much less often in PC-9/ZD2001 cells than in PC-9 cells or PC-9/ZD2001R cells. Expression of the inhibitor of apoptosis proteins c-IAP1 and c-IAP2 was induced by TNF-alpha in PC-9 and PC-9/ZD2001R cells but not in PC-9/ZD2001 cells. This weak effect of EGFR on Akt pathway might contribute to the TNF-alpha sensitivity of PC-9/ZD2001 cells. These results suggest that therapy with TNF-alpha would be effective in some cases of non-small-cell lung cancer that have acquired resistance to gefitinib.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/CASP3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CASP8 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 8,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Quinazolines,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/gefitinib
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| pubmed:status |
MEDLINE
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| pubmed:month |
Dec
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| pubmed:issn |
1078-0432
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| pubmed:author |
pubmed-author:AdachiMitsuruM,
pubmed-author:AndoKoichiK,
pubmed-author:HiroseTakashiT,
pubmed-author:HorichiNaoyaN,
pubmed-author:HosakaTakamichiT,
pubmed-author:InoueFumikoF,
pubmed-author:IshidaHirooH,
pubmed-author:KadofukuTsuyokiT,
pubmed-author:KurokiToshioT,
pubmed-author:NishioKazutoK,
pubmed-author:OhmoriTohruT,
pubmed-author:OkudaKentaroK,
pubmed-author:SaijoNagahiroN,
pubmed-author:ShiraiTakaoT
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| pubmed:issnType |
Print
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| pubmed:day |
15
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| pubmed:volume |
11
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
8872-9
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:16361577-Antineoplastic Agents,
pubmed-meshheading:16361577-Apoptosis,
pubmed-meshheading:16361577-Carcinoma, Non-Small-Cell Lung,
pubmed-meshheading:16361577-Caspase 3,
pubmed-meshheading:16361577-Caspase 8,
pubmed-meshheading:16361577-Caspases,
pubmed-meshheading:16361577-Cell Line, Tumor,
pubmed-meshheading:16361577-Drug Resistance, Neoplasm,
pubmed-meshheading:16361577-Enzyme Activation,
pubmed-meshheading:16361577-Humans,
pubmed-meshheading:16361577-Lung Neoplasms,
pubmed-meshheading:16361577-NF-kappa B,
pubmed-meshheading:16361577-Phosphorylation,
pubmed-meshheading:16361577-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:16361577-Quinazolines,
pubmed-meshheading:16361577-Receptor, Epidermal Growth Factor,
pubmed-meshheading:16361577-Signal Transduction,
pubmed-meshheading:16361577-Tumor Necrosis Factor-alpha
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| pubmed:year |
2005
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| pubmed:articleTitle |
Enhancement of sensitivity to tumor necrosis factor alpha in non-small cell lung cancer cells with acquired resistance to gefitinib.
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| pubmed:affiliation |
First Department of Internal Medicine and Institute of Molecular Oncology, Showa University, and Internal Medicine, Pharmacology Division, National Cancer Center Hospital, Tokyo, Japan.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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