Nuclear Factor-κB(NF-κB)/Interleukin-6 (IL-6) pathway activation confers resistance to docetaxel (D) in hormone-independent prostate cancer (HIPC)

Abstract

9630 Background: The activation of the NF-κB/IL-6 pathway is associated with androgen-independent progression of prostate cancer (PC) and may be implicated in resistance to chemotherapy. We investigated the role of NF-κB/IL-6 in the response to D in human PC cell lines and in HIPC pts, and the inhibition of NF-κB as a strategy to increase chemosensitivity in PC cells. Methods: The hormone-dependent (LNCaP) and hormone-independent (PC-3, DU-145) PC cells were treated with D+/- PS-1145 (specific IκB kinase 2 inhibitor). Cells were tested for activated p65/ NF-κB (western blot using anti-p65NLS antibody), IL-6 in culture medium (ELISA) and cell viability (MTT). Pts with metastatic HIPC receiving D were tested for plasma IL-6 (ELISA) before the start and every 3–4 weeks until the end of D. Results: In vitro sensitivity towards D was lower for p65NLS expressing and IL-6 producing cells (PC3, DU145) versus LNCaP, with lower p65NLS and no IL-6 production. Media IL-6 increased in both PC-3 and DU-145 after D trea...