Linked Life Data

17608771

Source:http://linkedlifedata.com/resource/pubmed/id/17608771

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2007-8-13
pubmed:abstractText
Paclitaxel (PTX) is an anticancer drug that is effective against a wide range of solid tumors. The effect of PTX on two human lung cancer cell lines, PC14PE6 and NCI-H441 cells, was examined in an orthotopically transplanted animal model with an in vivo imaging devise. Although PTX effectively suppressed tumor growth and improved survival rate in NCI-H441, it did not influence these in PC14PE6. In vitro experiments confirmed that PC14PE6 cells are resistant to PTX under normoxic conditions and that both cell lines were resistant to PTX under hypoxic conditions. It was found that the expression level of endogenous hypoxia inducible factor (HIF)-1alpha in PC14PE6 is much higher than that in NCI-H441 cells under normoxic conditions. Furthermore, sensitivity to PTX in these cell lines was reversed when HIF-1alpha expression was decreased by siRNA specific to HIF-1alpha in PC14PE6 and increased by overexpression of the exogenous HIF-1alpha gene in NCI-H441. These results suggest that HIF-1 influences the PTX sensitivity of these cells. The authors further examined beta-tubulin, a target molecule of PTX, with western blotting and immunohistochemical analysis in these cells. The expression level of beta-tubulin was comparable in these cells under both normoxic and hypoxic conditions while the distribution of beta-tubulin and cell morphology were changed according to HIF-1alpha expression levels, suggesting that HIF-1 influences the conformation and dynamics of microtubules. These data support the potential development of HIF-1 targeted approaches in combination with PTX, where drug resistance tends to contribute to treatment failure.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1347-9032
pubmed:author
pubmed:issnType
Print
pubmed:volume
98
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1394-401
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Hypoxia inducible factor-1 influences sensitivity to paclitaxel of human lung cancer cell lines under normoxic conditions.
pubmed:affiliation
Department of Radiation Oncology and Image-applied Therapy, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't