IL-32γ inhibits cancer cell growth through inactivation of NF-B and STAT3 signals

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IL-32γ inhibits cancer cell growth through inactivation of NF-B and STAT3 signals
J H Oh; M C Cho; J H Kim; S Y Lee; H J Kim; E S Park; J O Ban; J W Kang; D H Lee; J H Shim; S B Han; D C Moon; Young-Ho Park; Dae Yeul Yu; J M Kim; S H Kim; D Y Yoon; J T Hong
Bibliographic Citation
Oncogene, vol. 30, no. 30, pp. 3345-3359
Publication Year
Several studies have shown physiological functions of interleukin (IL)-32, a novel cytokine. However, the role of IL-32 in cancer development has not been reported. In this study, we showed that IL-32γ inhibited tumor growth in IL-32γ-overexpressing transgenic mice inoculated with melanoma as well as colon tumor growth in xenograft nude mice inoculated with IL-32γ- transfected colon cancer cells (SW620). The inhibitory effect of IL-32γ on tumor growth was associated with the inhibition of constitutive activated nuclear transcription factor-B (NF-B) and of signal transducer and activator of transcription 3 (STAT3). The expression of antiapoptotic, cell proliferation and tumor-promoting genes (bcl-2, X-chromosome inhibitor of apoptosis protein (IAP), cellular IAP and cellular FADD-like IL-1Β-converting enzyme-inhibitory protein, cyclin D), cyclin-dependent kinase 4, cycolooxygenase-2 and inducible nitric oxide synthase was decreased, whereas the expression of apoptotic target genes (caspase-3 and-9, bax) increased. In tumor, spleen and blood, the number of cytotoxic CD8 T cells and CD57 natural killer cells and the levels of IL-10 increased, but that of tumor necrosis factor-α (TNF-α), IL-1Β and IL-6 decreased. We also found that forced overexpression of IL-32γ inhibited colon cancer cell (SW620 and HCT116) growth accompanied with the inhibition of activated NF-B and STAT3 in vitro. In addition, when IL-32γ was knocked down by small interfering RNA (siRNA) or neutralized with an anti-IL-32γ antibody, IL-32γ-induced colon cancer cell growth inhibition, the IL-32γ-induced decrease of TNF-α, IL-1 and IL-6 production, and the increase of IL-10 production were abolished. However, siRNA of NF-B and STAT3 augmented IL-32γ-induced colon cancer cell growth inhibition. These findings indicate significant pathophysiological roles of IL-32γ in cancer development.
cytokineIL-32NF-κBSTAT3colon cancer
Springer-Nature Pub Group
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Ochang Branch Institute > Division of National Bio-Infrastructure > Futuristic Animal Resource & Research Center > 1. Journal Articles
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