THE BIOLOGICAL CHARACTERISTICS OF ADENOVIRUS-MEDIATED IL-18 GENE-MODIFIED MURINE COLORECTAL ADENOCARCINOMA CELL IN VIVO AND IN VITRO |
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Authors: | SONG Wen-gang LIU Shu-xun QU Xun YU Yi-zhi HE Long TANG Ling WANG Wen-ya ZHANG Ming-hui CAO Xue-tao Institute of Immunology Second Military Medical University Shanghai |
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Institution: | SONG Wen-gang,LIU Shu-xun,QU Xun 1,YU Yi-zhi,HE Long TANG Ling 2,WANG Wen-ya,ZHANG Ming-hui,CAO Xue-tao * Institute of Immunology,Second Military Medical University,Shanghai 200433 1 Department of Immunology,Taishan Medical College |
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Abstract: | Objective: Interleukin 18 (IL-18) is a strong activator of NK cells and promotes the generation of IL-2, IFN-(, and GM-CSF. In the present study, we constructed adenovirus encoding IL-18 gene (AdIL-18), and observed the biological characteristics of IL-18 gene-modified murine colorectal adenocarcinoma cell (CT26) in vivo and in vitro. Methods: Gene modification was mediated by adenovirus. The proliferation of the cells was determined by MTT and IL-18 was assayed by ELISA. The cytotoxicity of NK and CTL was detected by four-hour 51Cr release assay. Results: IL-18 gene modification had no effect on the proliferation and morphology of CT-26 cells in vitro, but the growth of IL-18-modified CT26 cells was obviously inhibited in vivo. In addition, although IL-18-modified CT26 cells could form tumor nodules in vivo as well as LacZ-modified CT26 cells or wild-type CT26 cells, the mean survival time of the mice inoculated with IL-18-modified CT26 cells was significantly prolonged as compared with that of control groups. Thus, the anti-tumor immune responses were induced in the group of mice inoculated with IL-18-modified CT26 cells, which might be related to the activation of NK cells and CTL. However, all the three groups ultimately died of tumor. Conclusion: IL-18-modified CT26 cells could induce the anti-tumor immune responses incompletely, which required other factors for effective anti-tumor responses. |
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Keywords: | IL-18 Gene therapy Adenovirus tumor |
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