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

在雄激素非依赖性人前列腺癌 PC3 模型中，通过靶向白细胞介素 6 的 RNA 干扰抑制肿瘤生长和对化疗敏感

• 批准号: 24791646
• 负责人: SAKAI Iori
• 金额: $ 2.25万
• 依托单位: Kobe University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-24791646/
• 关键词: 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

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.

利用shRNA技术抑制雄激素非依赖性（AI）人前列腺癌PC 3细胞产生IL 6，通过调节细胞凋亡和信号转导途径抑制其在体外和体内的生长。此外，由于在PC 3/shIL 6和NF κ B信号传导途径之间形成阳性自分泌环，多西他赛给药甚至对PC 3/shIL 6也未能诱导显著的细胞毒性作用。然而，硼替佐米和多西他赛联合治疗可以通过灭活NF κ B信号转导成功抑制多西他赛诱导的IL 6产生，从而令人满意地增强多西他赛的体内敏感性。这些发现表明，单独使用shRNA或与多西他赛和硼替佐米组合使用shRNA抑制IL-6分泌，通过抑制AI前列腺癌的生长和增强化疗敏感性而成为一种有吸引力的方法。

项目成果

ヒト前立腺癌細胞株 PC3 における IL-6 発現抑制の意義

抑制人前列腺癌细胞系PC3中IL-6表达的意义

Chemosensitization and inhibition of tumor growth by short hairpin RNA targeting interleukin-6 in androgen-independent human prostate cancer PC3 cells

短发夹 RNA 靶向白介素 6 对雄激素非依赖性人前列腺癌 PC3 细胞的化疗增敏和抑制肿瘤生长