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

应用shRNA技术抑制雄激素非依赖性(AI)人前列腺癌PC3细胞产生IL6可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。在PC3/shIL6和NFkB信号通路之间形成正向自分泌环路，多西紫杉醇甚至对PC3/shIL6也不能产生明显的细胞毒作用。而联合应用波特佐米和多西紫杉醇能成功抑制多西紫杉醇诱导的IL6的产生，使NFkB信号失活，从而提高多西紫杉醇的体内敏感性。这些发现表明，单独使用shRNA或与多西紫杉醇和Bortezomib联合使用抑制IL-6的分泌，通过抑制AI前列腺癌的生长和增强化疗敏感性，是一种有吸引力的方法。

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.