The impact of sex hormonal receptor signaling on radio-sensitivity in bladder cancer

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K18620
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Keio University
• Principal Investigator: Ide Hiroki 慶應義塾大学, 医学部(信濃町), 共同研究員 (70365360)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 膀胱癌 / 放射線 / 性ホルモン受容体シグナル

Outline of Final Research Achievements

At first, we confirmed the expression of Estrogen Receptor (ER)β in 5637 and T24, human bladder cancer cell lines. In in vitro experiments, tamoxifen and knockdown of ERβ enhanced the radio-sensitivity in these cells. Next, in in vivo experiments using female xenograft models (5637 and T24), the combination treatment of tamoxifen and radiotherapy showed the significant anti-tumor effect, compared to single treatment. Finally, microarray showed that the expressions of several DNA repair-related genes in 5637 cells treated with radiation in medium with estradiol(E2) were significantly higher than those in medium without E2.

Free Research Field

膀胱癌

Academic Significance and Societal Importance of the Research Achievements

転移のない浸潤性膀胱癌の標準治療として、膀胱全摘除術があがるが、侵襲度が高く高齢の患者に負担を強いること、尿路変更を要するため、術後のQOLが著しく低下する問題点があげられる。近年、化学療法併用放射線治療が膀胱全摘除術に匹敵するが、十分ではなく非奏功例の後治療が困難を極める。今回の実験で、性ホルモン受容体シグナルと放射線感受性の実験の関連が明らかになり、性ホルモン受容体阻害剤を併用することで膀胱癌における放射線感受性の増強が期待され、現状の問題点が解決される可能性がある。