Interleukin-6 is responsible for drug resistance and anti-apoptotic effects in prostatic cancer cells

• Published in: The Prostate 2004-07, Vol.60 (2), p.120-129
• Main Authors: Pu, Yeong-Shiau, Hour, Tzyh-Chyuan, Chuang, Shuang-En, Cheng, Ann-Lii, Lai, Ming-Kuen, Kuo, Min-Liang
• Format: Article
• Language: English
• Subjects: Acute-Phase Proteins - genetics; Acute-Phase Proteins - pharmacology; apoptosis; Apoptosis - drug effects; Apoptosis - genetics; bcl-X Protein; Bcl-xL; Biological and medical sciences; Blotting, Western; Cell Survival; cytotoxic agents; DNA-Binding Proteins - pharmacology; Drug Resistance, Neoplasm; Enzyme-Linked Immunosorbent Assay; Gene Expression Profiling; Gynecology. Andrology. Obstetrics; Humans; Interleukin-6 - pharmacology; Male; Male genital diseases; Medical sciences; Nephrology. Urinary tract diseases; Oligonucleotides, Antisense - therapeutic use; prostatic neoplasms; Prostatic Neoplasms - pathology; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-bcl-2 - pharmacology; Reverse Transcriptase Polymerase Chain Reaction; STAT3; STAT3 Transcription Factor; Trans-Activators - pharmacology; Tumor Cells, Cultured; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland
• ISSN: 0270-4137; 1097-0045
• DOI: 10.1002/pros.20057

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.