Innovative Challenge to Castration-resistant Prostate Cancer: Introduction of AR-dependent Hormone Sensitivity Reacquisition Factor

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K18127
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Fujita Health University
• Principal Investigator: Takahara Kiyoshi 藤田医科大学, 医学部, 准教授 (90418939)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: prostate cancer

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.

Free Research Field

Urology

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。