THE BIOLOGICAL CHARACTERISTICS OF ADENOVIRUS-MEDIATED IL-18 GENE-MODIFIED MURINE COLORECTAL ADENOCAR

来源 :Chinese Journal of Cancer Research | 被引量 : 0次 | 上传用户:JasonCrazy
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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. 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 viewed 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 were distinctly 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 an 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 Conclusion: The 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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