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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2005-3-15
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pubmed:abstractText |
5-Fluorouracil (5-FU) is commonly used to treat human colon cancers but resistance to this compound is frequently observed in clinics. To characterize mechanisms of resistance to 5-FU and to develop new strategies for overcoming it, we established two cell lines that were resistant to 5-FU but not other chemotherapeutic agents from parental 5-FU-sensitive cell lines. Western blot analysis revealed that these resistant cells overexpressed the proteins Bcl-XL, Bcl-Xs, and Bik, and further data showed that the cells were resistant to 5-FU-induced DNA damage and cell cycle disorder. However, in parental cells, enforced expression of Bcl-XL protein provided only limited protection from 5-FU-induced apoptosis and overexpression of Bcl-XL protein did not affect 5-FU-induced DNA damage or cell cycle changes; these findings suggested that overexpression of Bcl-XL protein was not the major contributor to 5-FU resistance in any of our cells lines. Even so, knockdown of Bcl-XL protein expression by Bcl-XL-specific small interfering RNA could inhibit proliferation more effectively in 5-FU-resistant cells than in 5-FU-sensitive cells, and the combination of Bcl-XL-specific small interfering RNA and 5-FU had additive effect on the inhibition of 5-FU-resistant cells. These results suggest that down-regulation of Bcl-XL protein expression might provide a new treatment strategy for human 5-FU-resistant colon cancer therapy.
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pubmed:grant |
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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/Apoptosis Regulatory Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/BCL2L1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/BIK protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Fluorouracil,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/bcl-X Protein
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1535-7163
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
4
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
451-6
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:15767554-Antineoplastic Agents,
pubmed-meshheading:15767554-Apoptosis Regulatory Proteins,
pubmed-meshheading:15767554-Blotting, Western,
pubmed-meshheading:15767554-Cell Line, Tumor,
pubmed-meshheading:15767554-Cell Proliferation,
pubmed-meshheading:15767554-Cell Survival,
pubmed-meshheading:15767554-Colonic Neoplasms,
pubmed-meshheading:15767554-Dose-Response Relationship, Drug,
pubmed-meshheading:15767554-Down-Regulation,
pubmed-meshheading:15767554-Drug Resistance, Neoplasm,
pubmed-meshheading:15767554-Flow Cytometry,
pubmed-meshheading:15767554-Fluorouracil,
pubmed-meshheading:15767554-Humans,
pubmed-meshheading:15767554-Inhibitory Concentration 50,
pubmed-meshheading:15767554-Luciferases,
pubmed-meshheading:15767554-Membrane Proteins,
pubmed-meshheading:15767554-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:15767554-RNA, Messenger,
pubmed-meshheading:15767554-RNA, Small Interfering,
pubmed-meshheading:15767554-S Phase,
pubmed-meshheading:15767554-Time Factors,
pubmed-meshheading:15767554-Transfection,
pubmed-meshheading:15767554-bcl-X Protein
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pubmed:year |
2005
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pubmed:articleTitle |
Bcl-XL small interfering RNA suppresses the proliferation of 5-fluorouracil-resistant human colon cancer cells.
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pubmed:affiliation |
Department of Thoracic and Cardiovascular Surgery, Unit 445, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, N.I.H., Extramural
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