Development of therapeutics targeting the Vav3 oncogene for castration-resistant prostate cancer

2014 Fiscal Year Final Research Report

• Project/Area Number: 24592397
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: Oita University
• Principal Investigator: NOMURA TAKEO 大分大学, 医学部, 客員研究員 (40347034)
• Co-Investigator(Kenkyū-buntansha): MIMATA Hiromitsu 大分大学, 医学部, 教授 (60219714)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 去勢抵抗性 / 低酸素 / Vav3 / アポトーシス / アンドロゲン受容体

Outline of Final Research Achievements

We examined Vav3 siRNA effects on cell proliferation and apoptosis in docetaxel-treated LNCaP cells under chronic hypoxia (LNCaPH). Interrupting Vav3 signaling using siRNA enhanced docetaxel-induced cell growth suppression compared with that induced by docetaxel alone by inhibition of Akt and ERK phosphorylation, resulting in AR phosphorylation inhibition. In addition to increased Bcl-2 phosphorylation through JNK signaling in response to docetaxel, si-Vav3 enhanced docetaxel-induced apoptosis through Bad dephosphorylation. Xenograft tumor growth was inhibited by si-Vav3/atelocollagen complex injection and combined use of si-Vav3 and docetaxel produced a greater effect than docetaxel alone.
Interrupting Vav3 signaling enhances docetaxel-induced apoptosis in LNCaP cells under chronic hypoxia by inhibiting the PI3K/Akt, ERK, and AR signaling pathways. Therapy targeting Vav3 in combination with docetaxel may have practical implications for managing castration-resistant prostate cancer.

Free Research Field

前立腺癌治療