| Project/Area Number |
20K18127
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 56030:Urology-related
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| Research Institution | Fujita Health University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2022: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
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| Keywords | prostate cancer / 前立腺癌 / 去勢抵抗性前立腺癌 / AR |
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| Outline of Research at the Start |
進行前立腺癌の一般的な手段であるアンドロゲン遮断療法は、その近接効果は著明である
が、多くの症例で数年以内に治療抵抗性の去勢抵抗性前立腺癌（CRPC castrationresistant prostate cancer）となる。2015年包括的OMICSデータにより、CRPC発現に関連する遺伝子の同定が明確化されつつある。本研究では、OMICSデータを踏まえ、CRPCのホルモン非依存性状態を引き起こす生物学的事象の早期解明を目的とする。
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| Outline of Final Research Achievements |
Using cell proliferation and Western blot analysis, we demonstrated that a-methylacyl-CoA racemase (AMACR) inhibition and docetaxel treatment, under androgen deprivation conditions, significantly reduced the proliferation of androgen receptor V7 (ARV7) positive cancer cells and decreased the levels of AR and ARV7 expression, possibly via downregulation of heat shock protein 27.
In vitro experiments indicated that the growth of LNCaP cells after combination therapy of alanine-serine-cysteine transporter 2 (ASCT2) siRNA and enzalutamide treatment was significantly reduced, compared to that following treatment with enzalutamide alone or ASCT2 siRNA transfection alone. After ASCT2 inhibition by siRNA transfection, the growth of 22Rv1 cells was significantly suppressed as compared with negative control siRNA via downregulation of ARV7 both in fetal bovine serum and androgen-deprivation conditions.
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| Academic Significance and Societal Importance of the Research Achievements |
今回の結果は、前立腺癌のホルモン抵抗性獲得メカニズムの解明に役立つ可能性があり、治療に難渋する進行性前立腺癌患者にとって有益と考えられる。
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