title: IL-33 acts as a foe to MIA PaCa-2 pancreatic cancer.
abstract: IL-33 is a member of the IL-1 family of cytokines, and no study has been performed to address its direct anti-tumor effect. This study is designed to investigate whether IL-33 has any direct effect on pancreatic cancer. Clonogenic survival assay, immunohistochemistry, TUNEL staining, proliferation, caspase-3 activity kits and RT-PCR were used to evaluate the effects of IL-33 on cell survival, proliferation and apoptosis of a pancreatic cancer cell line, MIA PaCa-2. We found that the percentage of colonies of MIA PaCa-2 cells, PCNA+ cells and the OD value of cancer cells were all decreased in the presence of IL-33. TUNEL+ cells and the relative caspase-3 activity in cancer cells were increased in the presence of IL-33. We further found that its anti-proliferative effect on cancer cells correlated with downregulation of pro-proliferative molecules cdk2 and cdk4 and upregulation of anti-proliferative molecules p15, p21 and p53. Its pro-apoptotic effect correlated with downregulation of anti-apoptotic molecule FLIP and upregulation of pro-apoptotic molecule TRAIL. These results suggest that IL-33 presents significant anti-tumor effects by inhibition of proliferation and induction of apoptosis of MIA PaCa-2 pancreatic cancer cells. Thus, strength of IL-33/ST2 signal pathway might be a promising way to treat pancreatic cancer.
authors.affiliation: Department of Microbiology, Immunology and Pathology, College of Osteopathic Medicine, Des Moines University, Des Moines, IA, 50312, USA. yujiang.fang@dmu.edu.|Department of Surgery, University of Missouri School of Medicine, Columbia, MO, 65212, USA. yujiang.fang@dmu.edu.
authors.forename: Yujiang
authors.initials: Y
authors.lastname: Fang
authors.affiliation: Department of Infectious Disease, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Microbiology, Immunology and Pathology, College of Osteopathic Medicine, Des Moines University, Des Moines, IA, 50312, USA.|The Affiliated Hospital of Xiangnan University, Chenzhou, Hunan, China.
authors.forename: Huaping
authors.initials: H
authors.lastname: Xiao
authors.affiliation: Department of Surgery, University of Missouri School of Medicine, Columbia, MO, 65212, USA.
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Cook
authors.affiliation: Department of Surgery, University of Missouri School of Medicine, Columbia, MO, 65212, USA.
authors.forename: Qian
authors.initials: Q
authors.lastname: Bai
authors.affiliation: Department of Surgery, University of Missouri School of Medicine, Columbia, MO, 65212, USA.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Herrick
authors.affiliation: Department of Microbiology, Immunology and Pathology, College of Osteopathic Medicine, Des Moines University, Des Moines, IA, 50312, USA.|Luohu Hospital, Shenzhen, China.
authors.forename: Xuhui
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Surgery, University of Missouri School of Medicine, Columbia, MO, 65212, USA.|Luohu Hospital, Shenzhen, China.
authors.forename: Chenglu
authors.initials: C
authors.lastname: Qin
authors.affiliation: Department of Surgery, University of Missouri School of Medicine, Columbia, MO, 65212, USA.
authors.forename: Ziwen
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of Surgery, University of Missouri School of Medicine, Columbia, MO, 65212, USA.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Wakefield
authors.affiliation: Department of Surgery, University of Missouri School of Medicine, Columbia, MO, 65212, USA.|Department of Surgery, South Texas Veterans Health Care System, 7400 Merton Minter Blvd, San Antonio, TX, 78229, USA.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Nicholl
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D006801:Humans; D000072179:Interleukin-1 Receptor-Like 1 Protein / Q000096:biosynthesis; D000067596:Interleukin-33 / Q000494:pharmacology*; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: C079241:IL1RL1 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33
keywords: Apoptosis; IL-33; Proliferation