Antitumor effects of interleukin-18 gene-modified hepatocyte cell line on implanted liver carcinoma  

作　　者：冷建杭 张立煌 姚航平 曹雪涛 

机构地区：[1]Central Laboratory,the First People's Hospital [2]Institute of Immunology,Zhejiang University [3]Iustitute of Immunology,the Second Military Medical University

出　　处：《Chinese Medical Journal》2003年第10期1475-1479,共5页中华医学杂志（英文版）

基　　金：Thisstudywassupportedby grantsfromtheNationalNaturalScienceFoundationofChina (No 3 0 12 10 0 2 )andNationalKeyBasicResearchProgramofChina (No .2 0 0 1CB5 10 0 0 2 )

摘　　要：Objective To investigate the antitumor effects of intrasplenically transplanted interleukin-18 (IL-18) gene-modified hepatocytes on murine implanted liver carcinoma. Methods Embryonic murine hepatocyte cell line (BNL-CL2) was transfected with a recombinant adenovirus encoding IL-18 and used as delivery cells for IL-18 gene transfer. Two cell lines,BNL-LacZ and BNL-CL2, were used as controls. One week after intrasplenic injection of C26 cells (colon carcinoma line),tumor-bearing syngeneic mice underwent the intrasplenic transplantation of IL-18 gene-modified hepatocyte cell line and were divided into treatment group (BNL IL-18) and control groups (BNL-LacZ and BNL-CL2 ). Two weeks later,the serum levels of IL-18,interferon-γ (IFN-γ),tumor necrosis factor-α (TNF-α) and nitric oxide (NO) in the implanted liver carcinoma-bearing mice were assayed,the cytotoxicity of murine splenic cytotoxic T-lymphocytes (CTLs) was measured,and the morphology of the hepatic tumors was studied to evaluate the antitumor effects of the approach. Results In the treatment group,the serum levels of IL-18,IFN-γ,TNF-α and NO increased significantly. The splenic CTL activity increased markedly ( P <0.01) ,accompanied by a substantial decrease in tumor volume and the percentage of tumor area and prolonged survival of liver carcinomo-being mice. Conclusions In vivo IL-18 expression by ex vivo manipulated cells with IL-18 recombinant adenovirus is able to exert potent antitumor effects by inducing a predominantly T-cell-helper type 1 (Th1) immune response. Intrasplenic transplantation of adenovirus-mediated IL-18 gene-modified hepatocytes could be used as a targeting treatment for implanted liver carcinoma.Objective To investigate the antitumor effects of intrasplenically transplanted interleukin-18 (IL-18) gene-modified hepatocytes on murine implanted liver carcinoma. Methods Embryonic murine hepatocyte cell line (BNL-CL2) was transfected with a recombinant adenovirus encoding IL-18 and used as delivery cells for IL-18 gene transfer. Two cell lines,BNL-LacZ and BNL-CL2, were used as controls. One week after intrasplenic injection of C26 cells (colon carcinoma line),tumor-bearing syngeneic mice underwent the intrasplenic transplantation of IL-18 gene-modified hepatocyte cell line and were divided into treatment group (BNL IL-18) and control groups (BNL-LacZ and BNL-CL2 ). Two weeks later,the serum levels of IL-18,interferon-γ (IFN-γ),tumor necrosis factor-α (TNF-α) and nitric oxide (NO) in the implanted liver carcinoma-bearing mice were assayed,the cytotoxicity of murine splenic cytotoxic T-lymphocytes (CTLs) was measured,and the morphology of the hepatic tumors was studied to evaluate the antitumor effects of the approach. Results In the treatment group,the serum levels of IL-18,IFN-γ,TNF-α and NO increased significantly. The splenic CTL activity increased markedly ( P <0.01) ,accompanied by a substantial decrease in tumor volume and the percentage of tumor area and prolonged survival of liver carcinomo-being mice. Conclusions In vivo IL-18 expression by ex vivo manipulated cells with IL-18 recombinant adenovirus is able to exert potent antitumor effects by inducing a predominantly T-cell-helper type 1 (Th1) immune response. Intrasplenic transplantation of adenovirus-mediated IL-18 gene-modified hepatocytes could be used as a targeting treatment for implanted liver carcinoma.

关 键 词：interleukin-18·gene therapy·intrasplenic transplantation·implanted liver carcinoma 

分 类 号：R735.7[医药卫生—肿瘤] R979.14[医药卫生—临床医学]