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New treatment strategy of refractory prostate cancer by regulation of androgen-androgen receptor axis and PI3K/Akt pathway

Research Project

Project/Area Number 25861449
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Urology
Research InstitutionKeio University

Principal Investigator

ISHIOKA KATSURA  慶應義塾大学, 医学部, 助教 (80573352)

Research Collaborator KOSAKA Takeo  慶応義塾大学, 医学部, 助教 (30445407)
KIKUCHI Eiji  慶応義塾大学, 医学部, 講師 (10286552)
MIYAJIMA Akira  慶応義塾大学, 医学部, 講師 (90245572)
OYA Mototsugu  慶応義塾大学, 医学部, 教授 (00213885)
Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsドセタキセル抵抗性前立腺癌細胞株 / アンドロゲン受容体阻害剤 / PI3K/mTOR阻害剤 / 抗腫瘍効果 / 併用効果
Outline of Final Research Achievements

Mutual exclusivity of androgen-androgen receptor axis (AR axis) and PI3K/Akt pathway by negative feedback is one of the contributing factor of resistance to treatment of prostate cancer, so we examined combination therapy of PI3K/mTOR inhibitor(NVP-BEZ235)and AR inhibitor(Abirateron and MDV3100). There is more expression of androgen receptor (AR) in C4-2AT6 than C4-2, and expression of AR increased by using NVP-BEZ235 dose-dependently. Secondly, we evaluated cell killing effectiveness of C42-AT6 by combination therapy using WST assay, then cell killing effectiveness increased by using Abirateron, though not increased by using MDV3100 unexpectedly. There showed effectiveness of combination therapy in LNCaP which is androgen sensitive prostate cancer cell line, so the experimental result suggest that both inhibitation of AR axis and PI3K/Akt pathway is not effective to prostate cancer cell line which achieved high grade of malignancy.

Report

(3 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report

URL: 

Published: 2014-07-25   Modified: 2019-07-29  

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