title: Adenovirus-mediated interleukin 21 gene transfer enhances antitumor immunity and reduces tumorigenicity of Hepa1-6 in mice.
abstract: In the present study, adenovirus-mediated interleukin 21 (Ad5-IL-21-EGFP) gene expression was induced in Hepa1-6 cells to investigate whether IL-21 was capable of enhancing antitumor immunity and reducing tumorigenicity of Hepa1-6 in a mouse model. Mice were inoculated intradermally into the right flank with Hepa1-6 cells or Hepa1-6 cells infected with Ad5 or Ad5-IL-21. Four weeks later, the mice were sacrificed humanely, and the tumor volume, tumor weight and mouse spleen index were measured. The levels of IL-21, IL-4 and interferon (IFN)-γ levels in mouse serum and tumor tissues were detected by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry. Cell counting kit-8 (CCK-8) assay was used to detect the killing ability of spleen T cells and natural killer (NK) cells, and the proliferation ability of T cells. The expression of IL-21 was confirmed by reverse transcription-polymerase chain reaction, western blot analysis and ELISA assay in Ad5-IL-21-EGFP-infected Hepa1-6 cells. The overexpression of IL-21 significantly reduced the tumorigenicity of Hepa1-6 cells. The tumor volumes and tumor weights in Ad5-IL-21-Hepa1-6 mice were much smaller than those in the Ad5-Hepa1-6 group and Hepa1-6 wild-type group. The immunohistochemistry and ELISA assay demonstrated that IL-21 and IFN-γ levels were much higher while the IL-4 level was much lower in the Ad5-IL-21-Hepa1-6 group than in the other two groups. CCK-8 assay revealed that the killing ability of NK cells and T cells, and the proliferation ability of T cells in Ad5-IL-21-Hepa1-6 mice were higher than in the other two groups; the spleen index of Ad5-IL-21-Hepa1-6 mice was also higher than in the other groups. The data had a significant difference (P<0.01). In conclusion, IL-21 reduces tumorigenicity of Hepa1-6 by a mechanism involving enhanced activation of cell-mediated immunity in tumor-bearing mice.
authors.affiliation: Department of Immunology, Weifang Medical University, Weifang, Shandong 261053, P.R. China.
authors.forename: Jiyu
authors.initials: J
authors.lastname: Ju
authors.affiliation: Department of Immunology, Weifang Medical University, Weifang, Shandong 261053, P.R. China.
authors.forename: Lina
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Immunology, Weifang Medical University, Weifang, Shandong 261053, P.R. China.
authors.forename: Dalin
authors.initials: D
authors.lastname: Di
authors.affiliation: Department of Immunology, Weifang Medical University, Weifang, Shandong 261053, P.R. China.
authors.forename: Weiling
authors.initials: W
authors.lastname: Xiao
authors.affiliation: Department of Immunology, Weifang Medical University, Weifang, Shandong 261053, P.R. China.
authors.forename: Meiyu
authors.initials: M
authors.lastname: Peng
authors.affiliation: Department of Immunology, Weifang Medical University, Weifang, Shandong 261053, P.R. China.
authors.forename: Yishuai
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Immunology, Weifang Medical University, Weifang, Shandong 261053, P.R. China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Fu
authors.affiliation: College of Pharmacy and Biological Science, Weifang Medical University, Weifang, Shandong 261053, P.R. China.
authors.forename: Chunling
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Department of Immunology, Weifang Medical University, Weifang, Shandong 261053, P.R. China.
authors.forename: Xuebin
authors.initials: X
authors.lastname: Qin
keywords: antitumor immunity; interleukin 21; liver cancer; tumorigenicity of Hepa1–6