期刊
CANCER IMMUNOLOGY IMMUNOTHERAPY
卷 64, 期 2, 页码 249-258出版社
SPRINGER
DOI: 10.1007/s00262-014-1630-z
关键词
N-3 PUFAs; IFN-gamma signaling; IL-18 binding protein; Prostate cancer cells
资金
- Canadian Institute for Health Research
- National Research Council Canada
- Canadian Breast Cancer Foundation-Atlantic
Prostate cancer cells can produce IL-18 binding protein (IL-18BP) in response to interferon-gamma (IFN-gamma), which may function to neutralize IL-18, an anti-tumor factor formerly known as IFN-gamma inducing factor. The consumption of n-3 polyunsaturated fatty acids (PUFAs) has been associated with a lower risk of certain types of cancer including prostate cancer, although the precise mechanisms of this effect are poorly understood. We hypothesized that n-3 PUFAs could modify IL-18BP production by prostate cancer cells by altering IFN-gamma receptor-mediated signal transduction. Here, we demonstrate that n-3 PUFA treatment significantly reduced IFN-gamma-induced IL-18BP production by DU-145 and PC-3 prostate cancer cells by inhibiting IL-18BP mRNA expression and was associated with a reduction in IFN-gamma receptor expression. Furthermore, IFN-gamma-induced phosphorylation of Janus kinase 1 (JAK1), signal transducers and activators of transcription 1 (STAT1), extracellular signal-regulated kinases 1/2 (ERK1/2), and P38 were suppressed by n-3 PUFA treatment. By contrast, n-6 PUFA had no effect on IFN-gamma receptor expression, but decreased IFN-gamma-induced IL-18BP production and IFN-gamma stimulation of JAK1, STAT1, ERK1/2, and JNK phosphorylation. These data indicate that both n-3 and n-6 PUFAs may be beneficial in prostate cancer by altering IFN-gamma signaling, thus inhibiting IL-18BP production and thereby rendering prostate cancer cells more sensitive to IL-18-mediated immune responses.
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