title: Effects on apoptosis and cell cycle arrest contribute to the antitumor             responses of interleukin-27 mediated by retrovirus in human pancreatic carcinoma             cells.
abstract: Interleukin (IL)-27, composed of p28 and Epstein-Barr virus-induced gene             3 (EBI3) subunits, has diverse functions in regulating immune systems. Human melanoma             cells have been shown to express both IL-27 receptor subunits, and growth inhibition             by IL-27 was detected. We investigated whether forced expression of the p28-linked             EBI3 gene in human pancreatic carcinoma cells (AsPC1) by retroviral vector would             produce IL-27-mediated antitumor effects and the related mechanisms. The data             demonstrated that AsPC1 cells expressed both IL-27 receptor subunits, and tumor             growth of AsPC1/IL-27 in mice was retarded compared with vector DNA-transduced             tumors and survival of the mice was prolonged. Expression of cytokines such as             interferon-γ, tumor necrosis factor-α and IL-1β in tumor specimens increased,             while the secretion of IFN-γ and TNF-α from spleen cells of mice bearing IL-27-transfected             tumors increased. Moreover, cell cycle arrest was induced in AsPC1/IL-27 inoculated             mice with upregulated p21 expression and downregulated survivin expression. The             appearance of apoptotic cells increased in tumor specimens of mice bearing IL-27-transfected             tumors compared with the mice bearing DNA-transfected tumors by confirming the             expression of apoptosis-related proteins and activated apoptotic pathways through             detection of cleaved PARP. These results suggest that transfection of the IL-27             gene into human pancreatic carcinoma cells could produce antitumor effects in vivo             and induction of cell cycle arrest and apoptosis could be the mechanism of IL-27             action in tumor regression.
authors.affiliation: Research Center, Department of Clinical Cell Therapy, the Fourth Hospital of Hebei Medical University and Hebei Cancer Institute, Shijiazhuang 050011, PR China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Liu
authors.forename: Jun
authors.initials: J
authors.lastname: Meng
authors.forename: Cong
authors.initials: C
authors.lastname: Zhang
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Duan
authors.forename: Lianmei
authors.initials: L
authors.lastname: Zhao
authors.forename: Shijie
authors.initials: S
authors.lastname: Wang
authors.forename: Baoen
authors.initials: B
authors.lastname: Shan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D059447:Cell Cycle Checkpoints / Q000235:genetics*; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D015870:Gene Expression; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D007378:Interleukins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D012190:Retroviridae / Q000235:genetics*; D014185:Transplantation, Isogeneic
chemical_list: D016207:Cytokines; C486767:Il27 protein, mouse; D007378:Interleukins