The function of MIG6 and the effect of combination treatment of MPA and HDAC inhibitor in endometrial cancer

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K20183
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Obstetrics and gynecology
• Research Institution: Shinshu University
• Principal Investigator: Ando Hirofumi 信州大学, 学術研究院医学系, 助教 (80722925)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 子宮内膜癌 / 黄体ホルモン療法 / ヒストン脱アセチル化酵素阻害薬 / 妊孕性温存療法 / MIG6 / 黄体ホルモン受容体

Outline of Final Research Achievements

Panobinostat (LBH 589), an HDAC inhibitor, enhances the expression of progesterone receptor (PR) mRNA (P<0.05) and protein in the PR-positive (Ishikawa) and PR-negative (HEC1B, AN3CA) endometrial cancer cell lines. Combination treatment of LBH589 and medroxyprogesterone acetate (MPA) synergistically enhances the expression of MIG6 mRNA, a downstream factor of PR, and synergistically suppresses cell proliferation/viability of those cell lines. In addition, the combination therapy of LBH589 and MPA synergistically suppresses the growth of the HEC1B-xenograft tumor in nude mice. In these tumors, positive staining of PR and MIG6 and reduction of Ki67-positive cells are observed by LBH589 administration. These results suggest that the combined administration of LBH589 may enhance the effect of MPA therapy and may lead to the extension of indications for fertility preservation therapy.

Free Research Field

産婦人科学

Academic Significance and Societal Importance of the Research Achievements

近年、日本では子宮内膜癌患者が急激に増加し、40歳未満の若年成人患者も増加傾向であり、酢酸メドロキシプロゲステロン（MPA）による妊孕性温存療法の重要性が増している。MPA療法の適応は筋層浸潤のないIA期で、黄体ホルモン受容体（PR）陽性率の高い類内膜癌Grade1に限定されており、病変完全消失率も55%と十分な効果とは言えず、黄体ホルモン療法の効果を高める治療法の開発が望まれる。本研究結果はHDAC阻害剤がMPA療法の効果を高め、同剤の併用により妊孕性温存療法の適応拡大につながる可能性を示したものであり、意義が大きい。