Metabolomic analysis for discovering new therapeutic target of ovarian cancer cells treated with paclitaxel

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K16826
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Obstetrics and gynecology
• Research Institution: Yamagata University
• Principal Investigator: Seino Manabu 山形大学, 医学部, 助教 (40594320)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: 卵巣癌 / 化学療法耐性 / メタボローム解析

Outline of Final Research Achievements

Ovarian cancer is most lethal gynecological cancer. The aim of this study is elucidated mechanism of acquiring chemoresisntance, especially paclitaxel in ovarian cancer cells.
We compared metabolic profiles and reactions to paclitaxel in both a wild type A2780, human ovarian cancer cell line, and A-PM3, a cell line derived from A2780 exposed to paclitaxel for three months, using a capillary electrophoresis CE-MS/MS system. Asparagine and aspartic acid concentrations in A-PM3 were higher than these in A2780. Metabolites related tricarboxylic acid (TCA) cycle in A2780 were elevated after treated with paclitaxel but were unchanged in A-PM3. Our data show that asparagine and aspartic acid concentrations in ovarian cancer cells exposed to paclitaxel are elevated. Asparagine and aspartic acid may be related to acquired resistance to paclitaxel and asparagine/aspartic acid metabolism may be targets for new ovarian cancer therapy.

Free Research Field

婦人科癌

Academic Significance and Societal Importance of the Research Achievements

卵巣癌の化学療法ではプラチナ系薬剤とタキサン系薬剤を用い、その多くが同時併用を行う。再発時には薬剤耐性を獲得している場合が多い。その際に問題となるのはプラチナ系薬剤に対する抵抗性であると考えられているが、タキサン系薬剤に対する抵抗性も注目されておりタキサン耐性克服は卵巣癌患者の予後改善に寄与すると考えられている (BMC Cancer, 2015; 15; 536)。卵巣癌のタキサン耐性獲得化機序についての報告は散見されるものの、実臨床に応用されているものはない。本課題の卵巣癌タキサン耐性獲得化におけるメタボローム解析は新規性のある研究で臨床的に大きな意義のあるものと考えている。