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 Type	Multi-year Fund
Research Field	Urology
Research Institution	Kobe 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.