腺病毒介导反义VEGF降低肿瘤诱导免疫抑制及增强IL-2的抗肿瘤效果

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。

Reduction of Immunosupression Induced by Tumor and Improvement of Anti-Tumor Effect of IL-2 through Adinovirus Mediated Antisense VEGF

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.