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Title: Interleukin-6 is responsible for drug resistance and anti-apoptotic effects in prostatic cancer cells. Author: Pu YS, Hour TC, Chuang SE, Cheng AL, Lai MK, Kuo ML. Journal: Prostate; 2004 Jul 01; 60(2):120-9. PubMed ID: 15162378. Abstract: 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.[Abstract] [Full Text] [Related] [New Search]