[关键词]
[摘要]
目的:本研究旨在探讨腺病毒介导的反义VEGF降低肿瘤诱导的免疫抑制及增强IL-2的抗肿瘤效果。方法:用反义VEGF修饰及反义VEGF与IL-2基因共同修饰MM45T,Li小鼠肝癌细胞,然后观察修饰后的肿瘤细胞的致瘤性;并在体内观察反义VEGF与IL-2基因诱导肝癌模型小鼠肿瘤细胞的凋亡,以及肿瘤组织中CD4^ ,CD8^ 细胞浸润情况。结果:反义VEGF降低了肝癌细胞MM45T.Li的致瘤性;增加了肿瘤组织周围CD4^ ,CD8^ 细胞浸润,改善了模型小鼠的免疫抑制状态,提高了IL-2抗肿瘤效果。结论:反义VEGF不仅可抑制新生血管的生成,而且可降低肿瘤诱导的免疫抑制,从而提高免疫系统对肿瘤细胞的识别,与IL-2免疫基因治疗相结合可明显提高对肿瘤的杀伤效果。
[Key word]
[Abstract]
Objectives: Use antisense VEGF to reduce the immunosuppression induced by tumor and enhance the antithumor effect of IL-2. Methods: After the MMT45.Li murine liver cancer cells were modified with antisense VEGF alone, or antisense VEGF combined with IL-2 gene, the tumorigenesis of modified MM45T.Li was studied. The apoptosis of cancer cell induced by antisense VEGF and IL-2 gene in vivo was also studied. The tumors were cryosmeared 3 weeks after the mice bearing tumor were treated correspondingly with Ad-antiVEGF or Ad-Il-2 or Ad-antiVEGF/IL-2 or Ad-lacZ, the immunohistochemical analysis of CD4 + , CD8 + was performed.Results: The tumorigenesis of MM45T. Li was reduced by antisense VEGF, and the number of CD4 + , CD8 + cell was increased in tumor tissue, and the immunosupression was also reduced; At the same time antisense VEGF also enhanced the antithumor effect of IL-2 gene.Conclusions: Antisense VEGF not only can inhibit the neovascularization, but also can reduce the immunosupression induced by tumor, and improve lymphocyte infiltration toward tumor site;when it was combined with Il-2,anti VEGF can enhance the antitumor effect greatly.
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[基金项目]
国家自然科学基金 ( 39870 77)资助