Therapeutic effect of gene-therapy in combination with local X-irradiation in a mouse malignant melanoma model

被引:30
作者
Jin, GH [1 ]
Jin, SZ [1 ]
Liu, Y [1 ]
Xu, RM [1 ]
Yang, JZ [1 ]
Pan, XN [1 ]
Liu, SZ [1 ]
机构
[1] Jilin Univ, Norman Bethume Hlth Sci Ctr, MH Radiobiol Res Unit, Immunobiol Lab, Changchun 130021, Peoples R China
基金
中国国家自然科学基金;
关键词
radiotherapy; gene-therapy; interleukin; 18; B7.1; Egr-1; promoter; anticancer mechanism;
D O I
10.1016/j.bbrc.2005.03.070
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Plasmid containing mIL-18 and B7.1 genes downstream of Egr-1 promoter was constructed and used in gene-radiotherapy on malignant melanoma in C57BL/6J mice implanted with B16 cells followed by exploration of the immunologic mechanism of the therapeutic effect. The treatment with plasmid pEgr-IL-18-B7.1 plus local X-irradiation showed more effective suppression of tumor growth than the treatment with radiation alone, pEgr-IL-18-B7.1 alone, or single gene pEgr-IL-18 (or pEgr-B7.1) combined with local X-irradiation. Anticancer immunity was found to be significantly upregulated in tumor-bearing mice treated with pEgr-IL-18-B7.1 plus local X-irradiation. IL-18 showed no direct killing effect on malignant melanoma cells in vitro, and the mechanism of the combined therapy with pEgr-IL-18-B7.1 and local X-irradiation was apparently related with the stimulation of host anticancer immunity by increased secretion of IL-18 and upregulated immunogenicity of the tumor cells by increased expression of B7.1 on their surface in addition to the direct effect of local X-irradiation on the tumor cells. (c) 2005 Published by Elsevier Inc.
引用
收藏
页码:975 / 981
页数:7
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