Document Detail


A demethylating agent enhances chemosensitivity to vinblastine in a xenograft model of renal cell carcinoma.
MedLine Citation:
PMID:  21479360     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Hiroki Iwata; Hiromi Sato; Rina Suzuki; Ryota Yamada; Saki Ichinomiya; Midori Yanagihara; Hiroyuki Okabe; Yuko Sekine; Tomohiro Yano; Koichi Ueno
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-04-06
Journal Detail:
Title:  International journal of oncology     Volume:  38     ISSN:  1791-2423     ISO Abbreviation:  Int. J. Oncol.     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-04-19     Completed Date:  2011-08-09     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  9306042     Medline TA:  Int J Oncol     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  1653-61     Citation Subset:  IM    
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
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MeSH Terms
Descriptor/Qualifier:
Animals
Antineoplastic Agents / pharmacology*,  therapeutic use
Azacitidine / analogs & derivatives,  pharmacology,  therapeutic use
Carcinoma, Renal Cell* / drug therapy
Cell Cycle / drug effects,  genetics
Cell Line, Tumor
Cell Proliferation / drug effects
Cyclin-Dependent Kinase Inhibitor p21 / genetics,  metabolism
DNA Methylation / genetics
DNA Modification Methylases / antagonists & inhibitors*
Drug Resistance, Neoplasm / drug effects*
Enzyme Inhibitors / pharmacology,  therapeutic use
Gene Expression Profiling
Gene Expression Regulation, Neoplastic / drug effects
Humans
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Promoter Regions, Genetic
Proteomics
Vinblastine / pharmacology*,  therapeutic use
Xenograft Model Antitumor Assays*
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/CDKN1A protein, human; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Enzyme Inhibitors; 320-67-2/Azacitidine; 776B62CQ27/decitabine; 865-21-4/Vinblastine; EC 2.1.1.-/DNA Modification Methylases

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