Source:http://linkedlifedata.com/resource/pubmed/id/17912235
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2007-12-21
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pubmed:abstractText |
Due to the prevalence of tumor chemoresistance, the clinical response of advanced non-small cell lung cancer (NSCLC) to chemotherapy is poor. We suppressed tumor resistance to doxorubicin (Dox) in A549 cells, a human NSCLC cell line, both in vitro and in vivo in a lung tumor xenograft model, using a novel adenoviral expression system to deliver an RNA aptamer (A-p50) that specifically inhibits nuclear factor-kappaB (NF-kappaB) activation. By achieving selective, targeted, and early inhibition of NF-kappaB activity, we demonstrate that NF-kappaB plays a critical role in Dox-induced chemoresistance by regulating genes involved in proliferation (Ki-67), response to DNA damage (GADD153), antiapoptosis (Bcl-XL), and pH regulation (CA9). This Dox-induced NF-kappaB activation and subsequent chemoresistance is dependent on expression of p53. We also demonstrate that NF-kappaB promotes angiogenesis in the presence of Dox via the hypoxia-inducible factor-1alpha/vascular endothelial growth factor (HIF-1alpha/VEGF) pathway, revealing a previously unknown mechanism of NSCLC resistance to Dox. These studies provide important insights into the mechanisms of Dox-induced chemoresistance, and they demonstrate a novel, effective, and clinically practical strategy for interfering with these processes.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1525-0024
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pubmed:author |
pubmed-author:ClaryBryan MBM,
pubmed-author:DewhirstMark WMW,
pubmed-author:GiangrandePaloma HPH,
pubmed-author:KontosChristopher DCD,
pubmed-author:LiuYingmiaoY,
pubmed-author:MiJingJ,
pubmed-author:RabbaniZahid NZN,
pubmed-author:ReddySrinevas KSK,
pubmed-author:SalahuddinFawzia KFK,
pubmed-author:SuZhenZ,
pubmed-author:SullengerBruce ABA,
pubmed-author:VilesKristiK,
pubmed-author:ZhangXiuwuX
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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 |
66-73
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pubmed:meshHeading |
pubmed-meshheading:17912235-Adenoviridae,
pubmed-meshheading:17912235-Animals,
pubmed-meshheading:17912235-Antibiotics, Antineoplastic,
pubmed-meshheading:17912235-Aptamers, Nucleotide,
pubmed-meshheading:17912235-Carcinoma, Non-Small-Cell Lung,
pubmed-meshheading:17912235-Cell Line, Tumor,
pubmed-meshheading:17912235-Doxorubicin,
pubmed-meshheading:17912235-Drug Delivery Systems,
pubmed-meshheading:17912235-Drug Resistance, Neoplasm,
pubmed-meshheading:17912235-Genetic Vectors,
pubmed-meshheading:17912235-Humans,
pubmed-meshheading:17912235-Lung Neoplasms,
pubmed-meshheading:17912235-Mice,
pubmed-meshheading:17912235-Mice, Inbred BALB C,
pubmed-meshheading:17912235-Mice, Nude,
pubmed-meshheading:17912235-NF-kappa B
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pubmed:year |
2008
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pubmed:articleTitle |
RNA aptamer-targeted inhibition of NF-kappa B suppresses non-small cell lung cancer resistance to doxorubicin.
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pubmed:affiliation |
Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA. mi001@duke.edu
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pubmed:publicationType |
Journal Article
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