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Inhibition of tumor growth and sensitization to chemotherapy by RNA interference targeting interleukin-6 in the androgen-independent human prostate cancer PC3 model

Research Project

Project/Area Number 24791646
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Urology
Research InstitutionKobe University

Principal Investigator

SAKAI Iori  神戸大学, 医学(系)研究科(研究院), 研究員 (20533772)

Co-Investigator(Kenkyū-buntansha) FUJISAWA Masato  神戸大学, 大学院・医学研究科, 教授 (30243314)
MIYAKE Hideaki  神戸大学, 大学院・医学研究科, 准教授 (60379435)
Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2013: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2012: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Keywords前立腺癌 / IL6 / siRNA / 去勢抵抗性前立腺癌 / 去勢抵抗性 / 抗癌剤耐性化 / IL-6
Research Abstract

Suppression of IL6 production by androgen independent (AI) human prostate cancer PC3 cells using shRNA technology inhibited their growth both in vitro and in vivo through the modulation of apoptotic and signal transduction pathways. Furthermore, the administration of docetaxel failed to induce marked cytotoxic effects even on PC3/shIL6 due to the formation of positive autocrine loops between PC3/shIL6 and NFkB signaling pathways. However, combined treatment with bortezomib and docetaxel could successfully suppress the docetaxel induced IL6 production via the inactivation of NFkB signaling, resulting in a satisfactory enhancement of docetaxel sensitivity in vivo. These findings suggest that inhibition of IL-6 secretion using shRNA, either alone or in combination with docetaxel and bortezomib, emerges as an attractive approach by suppressing growth and enhancing chemosensitivity in AI prostate cancer.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (2 results)

All Other

All Presentation (2 results)

  • [Presentation] ヒト前立腺癌細胞株 PC3 における IL-6 発現抑制の意義

    • Organizer
      第97回日本泌尿器科学会総会
    • Related Report
      2013 Final Research Report
  • [Presentation] Chemosensitization and inhibition of tumor growth by short hairpin RNA targeting interleukin-6 in androgen-independent human prostate cancer PC3 cells

    • Organizer
      105th AUA annual meeting
    • Related Report
      2013 Final Research Report

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Published: 2013-05-31   Modified: 2019-07-29  

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