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.
Pu
Yeong-Shiau
YS
Department of Urology, National Taiwan University, College of Medicine, Taipei, Taiwan.
Hour
Tzyh-Chyuan
TC
Chuang
Shuang-En
SE
Cheng
Ann-Lii
AL
Lai
Ming-Kuen
MK
Kuo
Min-Liang
ML
D000209:Acute-Phase Proteins / Q000235:genetics / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics*; D015153:Blotting, Western; D002470:Cell Survival; D004268:DNA-Binding Proteins / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D004797:Enzyme-Linked Immunosorbent Assay; D020869:Gene Expression Profiling; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D008297:Male; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use; D011471:Prostatic Neoplasms / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D051020:bcl-X Protein
D000209:Acute-Phase Proteins; C494811:BCL2L1 protein, human; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D016376:Oligonucleotides, Antisense; D019253:Proto-Oncogene Proteins c-bcl-2; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; D051020:bcl-X Protein