Association between TERT promoter mutation and vitamin A receptor in ovarian clear cell carcinoma

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K09282
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Chiba University
• Principal Investigator: Nishikimi Kyoko 千葉大学, 医学部附属病院, 助教 (00536302)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 卵巣癌 / TERTプロモーター

Outline of Final Research Achievements

When bexarotene, an RXR agonist, was added to an ovarian cancer cell line at concentrations of 10μM and 20μM for 48 hours, the number of cells decreased significantly and the mRNA level of hTERT decreased significantly by 37% and 6.4%, respectively. In addition, the Luciferase assay also showed a significant decrease in promoter activity due to the addition of bexarotene. It was revealed that the LDH activity in the culture supernatant was significantly increased at a concentration of 10μM or higher, and that bexarotene induced cell death.
From 4 hours after bexarotene stimulation, it was revealed that the pyrotosis markers caspase 4 and gasdermin E induce activation.

Free Research Field

卵巣癌

Academic Significance and Societal Importance of the Research Achievements

卵巣明細胞癌は漿液性癌よりも抗がん薬の奏効率が低く、治療に難渋するため、既存薬よりも有効な薬の開発が望まれている。ベキサロテンによる卵巣癌の細胞死誘導はこれまでに報告がなく、卵巣癌に対する新規治療薬としての応用が期待される。