Antitumor activity of IL-32 beta through the activation of lymphocytes, and the inactivation of NF-kappa B and STAT3 signals

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Title
Antitumor activity of IL-32 beta through the activation of lymphocytes, and the inactivation of NF-kappa B and STAT3 signals
Author(s)
H M Yun; J H Oh; J H Shim; J O Ban; K R Park; J H Kim; D H Lee; J W Kang; Young-Ho Park; Dae Yeul Yu; Y Kim; S B Han; D Y Yoon; J T Hong
Bibliographic Citation
Cell Death & Disease, vol. 4, pp. e640-e640
Publication Year
2013
Abstract
Cytokine and activation of lymphocytes are critical for tumor growth. We investigated whether interleukin (IL)-32β overexpression changes other cytokine levels and activates cytotoxic lymphocyte, and thus modify tumor growth. Herein, IL-32β inhibited B16 melanoma growth in IL-32β-overexpressing transgenic mice (IL-32β mice), and downregulated the expressions of anti-apoptotic proteins (bcl-2, IAP, and XIAP) and cell growth regulatory proteins (Ki-67 antigen (Ki-67) and proliferating cell nuclear antigen (PCNA)), but upregulated the expressions of pro-apoptotic proteins (bax, cleaved caspase-3, and cleaved caspase-9). IL-32β also inhibited colon and prostate tumor growth in athymic nude mice inoculated with IL-32β-transfected SW620 colon or PC3 prostate cancer cells. The forced expression of IL-32β also inhibited cell growth in cultured colon and prostate cancer cells, and these inhibitory effects were abolished by IL-32 small interfering RNA (siRNA). IL-10 levels were elevated, but IL-1β, IL-6, and tumor necrosis factor-alpha (TNF-α) levels were reduced in the tumor tissues and spleens of IL-32β mice, and athymic nude mice. The number of cytotoxic T (CD8 +) and natural killer (NK) cells in tumor tissues, spleen, and blood was significantly elevated in IL-32β mice and athymic nude mice inoculated with IL-32β-transfected cancer cells. Constituted activated NF-κB and STAT3 levels were reduced in the tumor tissues of IL-32β mice and athymic nude mice, as well as in IL-32β-transfected cultured cancer cells. These findings suggest that IL-32β inhibits tumor growth by increasing cytotoxic lymphocyte numbers, and by inactivating the NF-κB and STAT3 pathways through changing of cytokine levels in tumor tissues.
Keyword
IL-32βLymphocytesNF-κBSTAT3Tumor growth
ISSN
2041-4889
Publisher
Springer-Nature Pub Group
DOI
http://dx.doi.org/10.1038/cddis.2013.166
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of National Bio-Infrastructure > Futuristic Animal Resource & Research Center > 1. Journal Articles
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