Interleukin-6 Is Responsible for Drug Resistance and Anti-Apoptotic Effects in Prostatic Cancer Cells

BACKGROUND. Interleukin (IL)-6-mediated anti-apoptotic effects and drug- resistance mechanisms in prostate cancer cells were investigated. METHODS. IL-6 levels of PC-3 and LNCaP cells were studied by using ELISA. Protective effects of IL-6 on cytotoxic agent-induced apoptosis were studied by exogenous IL-6 in serum-starved PC-3 cells and by anti- sense IL-6 strategy. Western blotting and reverse transcription-polymerase chain reaction (RT-PCR) were used to determine IL-6 effects on Bcl-2 family proteins. Tetracycline-regulated Bcl-xL expression system and dominant negative STAT3 transfectants were used to study IL-6 signaling pathways and its anti-apoptosis effects. RESULTS. Exogenous IL-6 and anti-sense IL- 6 oligonucleotide treatment conferred resistance to cytotoxic agent- induced apoptosis. Among Bcl-2 family proteins, only Bcl-xL was evidently increased by IL-6 stimulation. The anti-apoptotic effect of IL-6 can be significantly attenuated by anti-sense bcl-xL transfection and partially abrogated in dominant negative STAT3 transfectants. CONCLUSIONS. IL-6 is a survival factor against cytotoxic agent-induced apoptosis through both STAT3 and bcl-xL pathways in prostate cancer cells. Prostate 60: 120-129, 2004. (C) 2004 Wiley-Liss, Inc.