Establishment of cisplatin-resistant ovarian yolk sac tumor cells and investigation of the mechanism of cisplatin resistance using this cell line

Kiyosumi Shibata, Tomokazu Umezu, Maiko Sakurai, Hiroaki Kajiyama, Eiko Yamamoto, Kazuhiko Ino, Akihiro Nawa, Fumitaka Kikkawa

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background: Cisplatin is used as a key drug for ovarian yolk sac tumor (YST), but relapse may occur. Details of the molecular mechanism responsible for cisplatin resistance remain unclear. Methods: We established cisplatin-resistant ovarian YST cells (NOY1-CR) from parent NOY1. To characterize these cells, we examined cross-resistance to other anticancer drugs. Then, cDNA microarray analysis was performed to quantify gene expression in NOY1 and NOY1-CR cells. The expression of several potential genes related to drug resistance was compared with parent cells by real-time PCR and Western blotting. Knockdown experiments using small interfering RNA (siRNA) were also performed to confirm the genetic association with drug resistance. Results: The IC50 for cisplatin of NOY1-CR was 22.3-fold higher than that for parent cells. NOY1-CR cells showed cross-resistance to some drugs, but not to VP-16 and bleomycin. Microarray analysis identified 315 up-regulated and 412 down-regulated genes in NOY1-CR cells. Knockdown of GSTA1, which was up-regulated in resistant cells, by GSTA1 siRNA restored cisplatin sensitivity in NOY1-CR cells. Conclusions: Our data suggest the molecular mechanisms of cisplatin resistance and show the potential for GSTA1 to become a novel therapeutic target for cisplatin-resistant ovarian YST.

Original languageEnglish
Pages (from-to)104-111
Number of pages8
JournalGynecologic and Obstetric Investigation
Volume71
Issue number2
DOIs
Publication statusPublished - 01-03-2011
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Reproductive Medicine
  • Obstetrics and Gynaecology

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