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目的探讨联合应用反义缺氧诱导因子1α(HIF1α)与B71基因治疗肿瘤的疗效。方法构建反义HIF1α和B71表达载体,用阳离子脂质体辅助,联合或单独导入肿瘤,观察肿瘤生长情况。采用免疫组化、蛋白印迹等方法检测基因表达,并进行血管密度评估。结果单独转染反义HIF1α的表达质粒可以阻断肿瘤缺氧诱导反应,下调血管内皮细胞生长因子的表达,抑制新生血管形成和肿瘤生长,肿瘤的血管密度由对照组的19.5±1.8降至12.4±2.3。联合应用反义HIF1α转染和B71可根除大的肿瘤。结论反义HIF1α基因治疗可以提高B71介导的抗肿瘤免疫治疗的疗效。
Objective To investigate the therapeutic effect of combined use of antisense hypoxia inducible factor 1α (HIF1α) and B71 gene in the treatment of tumors. Methods The antisense HIF1α and B71 expression vectors were constructed and were introduced into the tumor by cationic liposomes. The tumor growth was observed. Immunohistochemistry, Western blot and other methods to detect gene expression, and assessment of vascular density. Results The antisense HIF1α plasmid transfected alone could block the hypoxia-induced tumor response, down-regulate the expression of vascular endothelial growth factor, inhibit neovascularization and tumor growth. The tumor density decreased from 19.5 ± 1.8 in the control group to 12.4 ± 2.3. Co-application of antisense HIF1α transfection and B71 eradicates large tumors. Conclusion Antisense HIF1α gene therapy can enhance the efficacy of B71-mediated anti-tumor immunotherapy.