Mechanism of Prostate Cancer Growth Inhibition by AR Suppression Focusing on the SGLT2 Glucose Transport Pathway

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K18590
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Fukushima Medical University
• Principal Investigator: hoshi seiji 福島県立医科大学, 医学部, 病院助手 (70813137)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 前立腺癌 / 糖代謝 / SGLT2 / アンドロゲン受容体

Outline of Final Research Achievements

In prostate cancer, glucose transporters responsible for sugar uptake in cancer are generally considered to be under-expressed. Therefore, in this study, we focused on sodium-glucose transporter 2 (SGLT2), which has a different pathway, to elucidate the relationship between SGLT2 and suppression of cell growth by suppressing androgen receptor activity, and to explore its potential as a diagnostic marker and therapeutic target. The objective of this study was to explore the potential of SGLT2 as a diagnostic marker and therapeutic target. In this study, we evaluated the relationship between the regulation of SGLT2 by the androgen receptor, which is considered important for prostate cancer growth, and cell proliferation; SGLT2 expression was higher in androgen-independent prostate cancer cell lines, suggesting that androgen-independent regulation is the predominant mechanism, but SGLT2 suppression could inhibit cell proliferation.

Free Research Field

前立腺癌

Academic Significance and Societal Importance of the Research Achievements

前立腺癌において、アンドロゲン受容体の遮断は細胞増殖を抑制し、主に使用される治療薬の標的とされる。しかし治療過程で、アンドロゲン受容体の発現低下と代替経路の発現亢進により、薬剤耐性を獲得する症例が存在する。今回、SGLT2はアンドロゲン受容体の発現低下に伴い発現が亢進する可能性があり、今後アンドロゲン受容体遮断薬の治療予測因子や治療不応症例において新たな治療標的になる可能性が示唆された。SGLT2阻害薬は糖尿病の治療薬として、大きな有害事象なく投与できる薬剤であるため、臨床での使用が期待される。