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

冷建杭 张立煌 姚航平 曹雪涛

中华医学杂志(英文版)2003,Vol.116Issue(10):1475-1479,5.
中华医学杂志(英文版)2003,Vol.116Issue(10):1475-1479,5.

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

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

冷建杭 1张立煌 2姚航平 2曹雪涛3

作者信息

  • 1. Central Laboratory, the First People 's Hospital, Hangzhou 310006, China
  • 2. Institute of Immunology, Zhejiang University, Hangzhou 310031, China
  • 3. Iustitute of Immunology, the Second Military Medical University, Shanghai 200433, China
  • 折叠

摘要

Abstract

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

Key words

interleukin-18/gene therapy/intrasplenic transplantation/implanted liver carcinoma

分类

医药卫生

引用本文复制引用

冷建杭,张立煌,姚航平,曹雪涛..Antitumor effects of interleukin-18 gene-modified hepatocyte cell line on implanted liver carcinoma[J].中华医学杂志(英文版),2003,116(10):1475-1479,5.

基金项目

This study was supported by grants from the National Natural Science Foundation of China (No. 30121002) and National Key Basic Research Program of China (No. 2001CB510002). (No. 30121002)

中华医学杂志(英文版)

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