Leng Jianhang, Zhang Lihuang, Yao Hangping, Cao Xuetao
Central Laboratory, the First People's Hospital, Hangzhou 310006, China.
Chin Med J (Engl). 2003 Oct;116(10):1475-9.
To investigate the antitumor effects of intrasplenically transplanted interleukin-18 (IL-18) gene-modified hepatocytes on murine implanted liver carcinoma.
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-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha) 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.
In the treatment group, the serum levels of IL-18, IFN-gamma, TNF-alpha 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.
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.
探讨脾内移植白细胞介素-18（IL-18）基因修饰的肝细胞对小鼠移植性肝癌的抗肿瘤作用。
用编码IL-18的重组腺病毒转染胚胎小鼠肝细胞系（BNL-CL2），用作IL-18基因转移的递送细胞。两种细胞系BNL-LacZ和BNL-CL2用作对照。在脾内注射C26细胞（结肠癌细胞系）一周后，荷瘤同基因小鼠接受IL-18基因修饰的肝细胞系的脾内移植，并分为治疗组（BNL IL-18）和对照组（BNL-LacZ和BNL-CL2）。两周后，检测荷移植性肝癌小鼠血清中IL-18、干扰素-γ（IFN-γ）、肿瘤坏死因子-α（TNF-α）和一氧化氮（NO）水平，测定小鼠脾细胞毒性T淋巴细胞（CTL）的细胞毒性，并研究肝肿瘤形态以评估该方法的抗肿瘤作用。
治疗组血清中IL-18、IFN-γ、TNF-α和NO水平显著升高。脾CTL活性明显增强（P<0.01），同时肿瘤体积和肿瘤面积百分比大幅下降，荷肝癌小鼠生存期延长。
用IL-18重组腺病毒体外操作细胞在体内表达IL-18能够通过诱导主要为1型辅助性T细胞（Th1）免疫反应发挥强大的抗肿瘤作用。腺病毒介导的IL-18基因修饰的肝细胞脾内移植可作为移植性肝癌的靶向治疗方法。
