Linked Life Data

17470361

Source:http://linkedlifedata.com/resource/pubmed/id/17470361

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2007-5-15
pubmed:abstractText
Cisplatin (CDDP) and its analogues are widely used for the treatment of a variety of human solid tumors. However, the molecular mechanism of its action remains to be understood. Vascular endothelial growth factor (VEGF) is a potent inducer of angiogenesis and is upregulated in many human cancers. In this study we demonstrated that CDDP-inhibited VEGF expression in human ovarian cancer cells. We found that CDDP inhibited the VEGF reporter activity in a dose-dependent manner, indicating that CDDP-inhibited transcriptional activation of VEGF. We also found that: (1) luciferase activity mediated by the VEGF reporter containing a mutation of the HIF-1 binding site was much lower than that of the reporter containing a wild-type HIF-1 binding site in ovarian cancer cells, thus confirming that HIF-1 is a major transcriptional regulator of VEGF expression; and that (2) CDDP greatly inhibited VEGF reporter activity containing the wild-type but not the mutant HIF-1 binding site. This result indicates that CDDP-inhibited VEGF transcriptional activation specifically by decreasing HIF-1 activity. Co-transfection of a dominant negative construct of HIF-1 inhibited VEGF reporter activity in ovarian cancer cells. CDDP-inhibited VEGF transcriptional activation specifically through the expression of HIF-1alpha, but not HIF-1beta. We demonstrated that VEGF receptor KDR was expressed in ovarian cancer cells, and that CDDP-inhibited VEGF expression was linked with cellular apoptosis, which was rescued by VEGF treatment. These results suggest a novel mechanism of CDDP's anti-tumor activity in ovarian cancer cells via HIF-1 expression and VEGF transcriptional activation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0006-291X
pubmed:author
pubmed:issnType
Print
pubmed:day
22
pubmed:volume
358
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
92-8
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Mechanism of vascular endothelial growth factor expression mediated by cisplatin in human ovarian cancer cells.
pubmed:affiliation
Laboratory of Reproductive Medicine, Cancer Center, Nanjing Medical University, Nanjing 210029, Jiangsu, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural