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Interleukin‐6 is responsible for drug resistance and anti‐apoptotic effects in prostatic cancer cells
Author(s) -
Pu YeongShiau,
Hour TzyhChyuan,
Chuang ShuangEn,
Cheng AnnLii,
Lai MingKuen,
Kuo MinLiang
Publication year - 2004
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20057
Subject(s) - apoptosis , cytotoxic t cell , lncap , prostate cancer , stat3 , transfection , cancer research , interleukin , biology , microbiology and biotechnology , immunology , cell culture , cancer , medicine , cytokine , in vitro , biochemistry , genetics
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.