Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2011-4-19
pubmed:abstractText
Renal cell carcinoma (RCC) is resistant to chemo-therapy partly due to the overexpression of the P-glycoprotein. Several tumor suppressor genes have been reported to be silenced by hypermethylation of the promoter region in RCC. We recently reported that the in vitro cytotoxicity of vinblastine (VBL) was enhanced by pre-treatment with the demethylating agent, 5-aza-2'-deoxycytidine (Aza), in the RCC cell line, Caki-1. In this study, we investigated the combined effect of Aza and VBL in a Caki-1 xenograft model and in other RCC cell lines in vitro. In the xenograft model, tumor volume and weight were significantly suppressed in the co-treatment group, compared to the control, and the expressions of P-glycoprotein, Bcl-2 and cyclin B1 were reduced. Thus, this combined effect could be mediated by the accumulation of intracellular VBL and the enhancement of apoptosis and cell cycle arrest. More-over, the cytotoxicity of VBL was enhanced in vitro in three RCC cell lines by Aza treatment. These findings suggest that the combination treatment with Aza and VBL is effective against RCC.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1791-2423
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
38
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1653-61
pubmed:meshHeading
pubmed-meshheading:21479360-Animals, pubmed-meshheading:21479360-Antineoplastic Agents, pubmed-meshheading:21479360-Azacitidine, pubmed-meshheading:21479360-Carcinoma, Renal Cell, pubmed-meshheading:21479360-Cell Cycle, pubmed-meshheading:21479360-Cell Line, Tumor, pubmed-meshheading:21479360-Cell Proliferation, pubmed-meshheading:21479360-Cyclin-Dependent Kinase Inhibitor p21, pubmed-meshheading:21479360-DNA Methylation, pubmed-meshheading:21479360-DNA Modification Methylases, pubmed-meshheading:21479360-Drug Resistance, Neoplasm, pubmed-meshheading:21479360-Enzyme Inhibitors, pubmed-meshheading:21479360-Gene Expression Profiling, pubmed-meshheading:21479360-Gene Expression Regulation, Neoplastic, pubmed-meshheading:21479360-Humans, pubmed-meshheading:21479360-Male, pubmed-meshheading:21479360-Mice, pubmed-meshheading:21479360-Mice, Inbred BALB C, pubmed-meshheading:21479360-Mice, Nude, pubmed-meshheading:21479360-Promoter Regions, Genetic, pubmed-meshheading:21479360-Proteomics, pubmed-meshheading:21479360-Vinblastine, pubmed-meshheading:21479360-Xenograft Model Antitumor Assays
pubmed:year
2011
pubmed:articleTitle
A demethylating agent enhances chemosensitivity to vinblastine in a xenograft model of renal cell carcinoma.
pubmed:affiliation
Department of Geriatric Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan. hirokiiwata@graduate.chiba-u.jp
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't