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Epigenetics in etoposide-resistant tumor cells

Research Project

Project/Area Number 13670848
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionNippon Medical School

Principal Investigator

ASANO Takeshi  Nippon Medical School, Assis Prof, 医学部, 助教授 (70277490)

Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2003: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2002: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2001: ¥700,000 (Direct Cost: ¥700,000)
KeywordsTopoisomerase / drug resistance / epigenetic / etoposide / エトポシド / メチレーション / 薬剤耐性 / メチル化 / エピジェネティクス
Research Abstract

K562/MX2 cells were more resistant to MX2 than the parent cells, also showed cross-resistance to etoposide, and doxorubicin. P-glycoprotein expression was identical to K562/P and K562/MX2. MRP1 expression in K562/MX2 is slightly higher than in K562/P. Accumulation of MX2 was slightly lower than in K562/P. Topoisomerase (Topo) IIα protein in K562/MX2 cells were lower of those in K562/P cells by immunoblot analysis as well as decreased expression of the Topo IIα mRNA in K562/MX2 cells. Topo II catalytic activity was also reduced in the nuclear extract from K562/MX2 cells compared with K562/P cells. Increased methylated CpG of Topo IIα gene was observed in K562/MX2 cells compared to parent line by bisulfite modified sequence and methylation specific restriction enzyme analysis. To overcome the drug resistance to MX2, and etoposide, we examined 5-Aza-2'-deoxycytidine(5AZ), which is a demethylating agent, treatment in K562/MX2 cells. 5AZ treatment increased Topo IIα mRNA expression in K562/MX2 cells, but not in K562/P cells, as well as increased cytotoxicity against MX2 and etoposide. The methylated CpG was decreased in K562/MX2 cells after 5AZ treatment. We concluded that the mechanism of drug resistance to MX2 as well as etoposide in K562/MX2 cells might contribute to decreased expression of Topo IIα gene with increased methylation of the gene and 5AZ treatment could be a novel treatment in etoposide resistant cell line, K562/MX2.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report

URL: 

Published: 2001-04-01   Modified: 2016-04-21  

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