摘要
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 synergistic effects of antisense HIF-1α gene therapy combined with B7-1-mediated immunotherapy on cancer treatment. Methods Antisense HIF-1α and B7-1 expression vector were constructed. Lymphoma cells EL-4 were injected subcutaneously into C57BL/6 mice and transplanted lymphomas were established. The mice received either antisense HIF-1α, B7-1, or a combinational agent,complexed with DOTAP cationic liposomes. The tumor growth in the mice was monitored. Expression of HIF-1α,B7-1 and VEGF were detected by immunohistochemistry and Westem blotting. The tumor blood vessels were immunostained with CD 3 1 - antibodies and the tumor vascular density was assessed by light microscopy. Results Gene transfer of plasmid expressing the encoded antisense HIF-1α inhibited VEGF expression and reduced vascular density in the tumors, eradicated tumors in diameter smaller than O. 1 cm and only retarded the growth of larger tumors. Whereas combination of antisense HIF-1α gene therapy and B7-1 immunotherapy eradicated all tumors in diameter of O. 4 cm. Conclusion Antisense HIF-1α blocks tumor hypoxia pathway by downregnlating VEGF expression, reduction of vascular density and enhances BT-l-mediated immunotherapy. Strategies that target HIF-1 may have therapeutic potential in cancer treatment and are worthy of further studying.
出处
《中华肿瘤杂志》
CAS
CSCD
北大核心
2005年第7期404-407,共4页
Chinese Journal of Oncology
基金
国家自然科学基金资助项目(30471681
30170916)
