Adenovirus‑mediated interleukin 21 gene transfer enhances antitumor immunity and reduces tumorigenicity of Hepa1‑6 in mice
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- Published online on: September 15, 2016 https://doi.org/10.3892/ol.2016.5140
- Pages: 3749-3754
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Copyright: © Ju et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
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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.
