Interleukin-6 is responsible for drug resistance and anti-apoptotic effects in prostatic cancer cells
Journal
Prostate
Journal Volume
60
Journal Issue
2
Pages
120-129
Date Issued
2004
Author(s)
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. ? 2004 Wiley-Liss, Inc.
SDGs
Other Subjects
antineoplastic agent; complementary DNA; cytotoxic agent; interleukin 6; oligonucleotide; protein bcl 2; protein bcl xl; STAT3 protein; tetracycline; apoptosis; article; cancer cell; cell protection; cell survival; controlled study; drug resistance; drug response; enzyme linked immunosorbent assay; human; human cell; priority journal; prostate cancer; reverse transcription polymerase chain reaction; serum; signal transduction; Western blotting; Acute-Phase Proteins; Apoptosis; bcl-X Protein; Blotting, Western; Cell Survival; DNA-Binding Proteins; Drug Resistance, Neoplasm; Enzyme-Linked Immunosorbent Assay; Gene Expression Profiling; Humans; Interleukin-6; Male; Oligonucleotides, Antisense; Prostatic Neoplasms; Proto-Oncogene Proteins c-bcl-2; Reverse Transcriptase Polymerase Chain Reaction; STAT3 Transcription Factor; Trans-Activators; Tumor Cells, Cultured
Type
journal article