The therapeutic strategy toward overcoming drug resistance of gynecologic cancers utilizing high throughput screening.

2014 Fiscal Year Final Research Report

• Project/Area Number: 24390375
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Tohoku University
• Principal Investigator: YAEGASHI Nobuo 東北大学, 医学(系)研究科(研究院), 教授 (00241597)
• Co-Investigator(Kenkyū-buntansha): TOYOSHIMA Masafumi 東北大学, 大学院医学系研究科, 非常勤講師 (70451581)
• Co-Investigator(Renkei-kenkyūsha): NAGASE Satoru 山形大学, 医学部, 教授 (00292326) ; SUZUKI Fumihiko 東北大学, 大学院医学系研究科, 助教 (20400343)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: スクリーニング / 薬剤耐性 / 婦人科がん / 化学療法 / シスプラチン

Outline of Final Research Achievements

The purpose of this study is to search the molecules that can cancel the cisplatin resistance of cancer cells. We explore the molecules that show a synthetic lethal effect with a small amount of CDDP administration in a high-throughput screening using siRNA library consisting of 6650 genes. As a result, a strong expression of TIE-1 was found to be decrease the sensitivity toward cisplatin in several ovarian cancer cell lines. The relationship among TIE-1, ovarian cancer and/or drug resistance has not been reported. In order to examine the significance of TIE-1 expression in ovarian cancer patients, in silico analysis was carried out. We confirmed that TIE-1 high expression group has a significantly poor prognosis by examination of the overall survival in 1582 ovarian cancer patients. Furthermore, we confirmed that apoptosis and γH2AX expressions, a marker for DNA-double strand breaks, were significantly decreased during CDDP administration in TIE-1 over-expressed cells.

Free Research Field

産婦人科学