Liu Shuxun

The biological characteristics of adenovirus-mediated il-18 gene-modified murine colorectal adenocarcinoma cellin vivo andin vitro

Objective: Interleukin 18 (IL-18) is a strong activator of NK cells and promotes the generation of IL-2, IFN-γ 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 andin 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-hour51Cr release assay. Results: IL-18 gene modification had no effect on the proliferation and morphology of CT-26 cellsin vitro, but the growth of IL-18-modified CT26 cells was obviously inhibitedin vivo. In addition, although IL-18-modified CT26 cells could form tumor nodulesin 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.Objective: Interleukin 18 (IL-18) is a strong activator of NK cells and promotes the generation of IL-2, IFN-γ 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 andin 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-hour51Cr release assay. Results: IL-18 gene modification had no effect on the proliferation and morphology of CT-26 cellsin vitro, but the growth of IL-18-modified CT26 cells was obviously inhibitedin vivo. In addition, although IL-18-modified CT26 cells could form tumor nodulesin 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.