title: Antitumor activity of IL-32β through the activation of lymphocytes, and the inactivation of NF-κB and STAT3 signals.
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.
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, Republic of Korea.
authors.forename: H-M
authors.initials: HM
authors.lastname: Yun
authors.forename: J H
authors.initials: JH
authors.lastname: Oh
authors.forename: J-H
authors.initials: JH
authors.lastname: Shim
authors.forename: J O
authors.initials: JO
authors.lastname: Ban
authors.forename: K-R
authors.initials: KR
authors.lastname: Park
authors.forename: J-H
authors.initials: JH
authors.lastname: Kim
authors.forename: D H
authors.initials: DH
authors.lastname: Lee
authors.forename: J-W
authors.initials: JW
authors.lastname: Kang
authors.forename: Y H
authors.initials: YH
authors.lastname: Park
authors.forename: D
authors.initials: D
authors.lastname: Yu
authors.forename: Y
authors.initials: Y
authors.lastname: Kim
authors.forename: S B
authors.initials: SB
authors.lastname: Han
authors.forename: D-Y
authors.initials: DY
authors.lastname: Yoon
authors.forename: J T
authors.initials: JT
authors.lastname: Hong
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D005260:Female; D045325:HCT116 Cells; D006801:Humans; D007378:Interleukins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D019394:Ki-67 Antigen / Q000378:metabolism; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology; D014183:Transplantation, Heterologous; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D016207:Cytokines; C496971:IL32 protein, human; D007378:Interleukins; D019394:Ki-67 Antigen; D016328:NF-kappa B; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; D051028:bcl-2-Associated X Protein; D053148:Caspase 3; D053453:Caspase 9