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

点击翻译按钮获取中文摘要

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.