Development of novel therapeutic strategies based on metabolomics analysis of uterine serous carcinoma

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K10699
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Yamagata University
• Principal Investigator: Nagase Satoru 山形大学, 医学部, 教授 (00292326)
• Co-Investigator(Kenkyū-buntansha): 鈴木 史彦 東北大学, 医学系研究科, 助教 (20400343) ; 太田 剛 山形大学, 医学部, 講師 (50375341) ; 清野 学 山形大学, 医学部, 助教 (40594320)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 子宮体部漿液性癌 / メタボローム解析 / パクリタキセル耐性 / スルファサラジン / フェロトーシス

Outline of Final Research Achievements

First, we examined metabolomic profile in USC cells by analysis using a capillary electrophoresis CE-MS/MS system. The concentration of GSH, Glucose-6-phosphate and ribose-5-phasphate in the PTX-1 cells was higher than that of USPC-1 cells. Next, we investigated the effect of the xCT inhibitor sulfasalazine (SAS) on cytotoxicity in paclitaxel-sensitive and -resistant USC cell lines. The results of proliferation and cell-death assays showed that SAS enhanced the efficacy of paclitaxel in both paclitaxel-sensitive and -resistant cell lines. Immunoblotting analysis and experiments conducted using ferroptosis inhibitors revealed that SAS-mediated cell death was induced through ferroptosis, and not apoptosis, in paclitaxel-resistant cells. Collectively, our findings indicate that xCT inhibition can overcome resistance to paclitaxel, and could thus represent a candidate novel treatment for patients with recurrent chemotherapy-resistant USC.

Free Research Field

婦人科腫瘍学