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

Research Project

Project/Area Number 19K18590
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 56030:Urology-related
Research InstitutionFukushima 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
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2019: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords前立腺癌 / 糖代謝 / SGLT2 / アンドロゲン受容体 / 去勢抵抗性前立腺癌
Outline of Research at the Start

本研究では、ヒトmHSPC前立腺癌細胞株(LNCaP,22RV-1)およびヒトホルモン抵抗性前立腺癌細胞株(PC3,Du145)を用いて、SGLT2の発現評価を行い、SGLT2阻害・過剰発現による細胞増殖の変化およびアンドロゲン受容体活性の変化の評価を行う。またmHSPC細胞株に対しアンドロゲン受容体阻害薬であるBicalutamide(BCL)を使用した際のSGLT2の発現変化および腫瘍の糖代謝について評価する。加えてSGLT2阻害・過剰発現下でのBCLの効果について評価をおこなうことで、SGLT2がアンドロゲン遮断療法に与える影響について検討する。

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.

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。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (1 results)

All 2021

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results)

  • [Journal Article] Upregulation of glucocorticoid receptor‐mediated glucose transporter 4 in enzalutamide‐resistant prostate cancer2021

    • Author(s)
      Hoshi Seiji、Meguro Satoru、Imai Hitomi、Matsuoka Yuta、Yoshida Yuki、Onagi Akihumi、Tanji Ryo、Honda‐Takinami Ruriko、Matsuoka Kanako、Koguchi Tomoyuki、Hata Junya、Sato Yuichi、Akaihata Hidenori、Kataoka Masao、Ogawa Soichiro、Kojima Yoshiyuki
    • Journal Title

      Cancer Science

      Volume: 112 Issue: 5 Pages: 1899-1910

    • DOI

      10.1111/cas.14865

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research

URL: 

Published: 2019-04-18   Modified: 2023-01-30  

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