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- Title
IL-32γ inhibits cancer cell growth through inactivation of NF-κB and STAT3 signals.
- Authors
Oh, J H; Cho, M-C; Kim, J-H; Lee, S Y; Kim, H J; Park, E S; Ban, J O; Kang, J-W; Lee, D-H; Shim, J-H; Han, S B; Moon, D C; Park, Y H; Yu, D-Y; Kim, J-M; Kim, S H; Yoon, D-Y; Hong, J T
- Abstract
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-κB (NF-κB) 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-κB 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-κB and STAT3 augmented IL-32γ-induced colon cancer cell growth inhibition. These findings indicate significant pathophysiological roles of IL-32γ in cancer development.
- Subjects
INTERLEUKINS; COLON cancer; CANCER cell growth; NF-kappa B; CYTOKINES; CYCLIN-dependent kinases; LABORATORY mice; GENE expression
- Publication
Oncogene, 2011, Vol 30, Issue 30, p3345
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/onc.2011.52