目的： 探讨体内非靶向转染表达重组FN多肽CH50对肿瘤的抑制作用及其相关机制。方法： BALB/c小鼠接种肝癌细胞后，实验组采用基于流体动力学方法体内非靶向转染CH50真核表达质粒，对照组分别注射对照质粒或生理盐水。接种后观察肿瘤生长情况；RT-PCR检测治疗过程中肿瘤局部组织B7-1、B7-H1等基因的表达变化；流式细胞术检测分析肿瘤局部T淋巴细胞的数量。结果： 体内非靶向基因转染表达CH50对肿瘤产生显著的抑制作用；肿瘤组织中B7-1、B7-H1等基因的表达随着肿瘤生长而上调；CH50治疗后可使B7-1/ B7-H1及B7-1/ B7-DC的比值显著增高，同时显著抑制IL-10和TGF-β基因的表达；CH50直接作用于瘤细胞可导致TGF-β基因表达下调；治疗组的肿瘤组织TIL数量显著高于对照组。结论： 非靶向转染表达CH50可有效抑制肿瘤生长，对肿瘤微环境中免疫基因表达的调节是其作用机制的重要方面。

Objective: To investigate the inhibitory effect of in vivo non-targeting transfection of recombinant fibronectin polypeptide CH50 against tumors and to study the related mechanisms. Methods: After inoculated with tumor cells, BALB/c mice were injected with CH50 plasmids, control plasmids, and normal saline separately. The growth of the tumor was observed; the expression of genes (such as B7-1, B7-H1 etc.) in tumor tissues was detected by RT-PCR; and the count of T lymphocytes in local tumor tissues was analyzed by flow cytometry. Results: The tumor growth was obviously suppressed by in vivo CH50 expression. The expression of genes (B7-1 and B7-H1) was up-regulated along with the growth of tumor. CH50 increased the ratios of B7-1/B7-H1 and B7-1/B7-DC and suppressed the up-regulation of IL-10 and TGF-β genes. The direct action of CH50 on H22 cells resulted in the down-regulatoin of TGF-β gene. The count of T lymphocytes in tumor tissues of CH50 treatment group was significantly higher than that in other groups. Conclusion: Expression of CH50 by non-targeting transfection can effectively inhibit the growth of tumor; the regulation of the immuno-regulatory genes in tumor microenvironment is an important part of the treatment mechanism of CH50.

国家重点基础研究发展（973）计划资助项目（No.2002CB513100）