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目的:研究白细胞介素-24(IL-24)增强溶瘤腺病毒(CRAd)ZD55抗白血病作用的机制。方法:用流式细胞仪检测ZD55对白血病细胞株Mutz-1的感染率;分别用ZD55、ZD55-IL-24和携带IL-24的非增殖型腺病毒(Ad-IL-24)处理白血病细胞(实验组),对照组为PBS。Western blot检测CRAd对白血病细胞血管内皮生长因子(VEGF)蛋白表达的影响;用免疫组化检测Mutz-1白血病荷瘤模型经CRAd治疗后肿瘤病理组织CD31和VEGF表达。结果:用10、100病毒感染复数(MOI)的ZD55感染白血病细胞48 h,感染率分别为5.1%和42.3%。ZD55-IL-24使VEGF蛋白表达显著下降,而Ad-IL-24感染后未能使VEGF明显下调。ZD55对VEGF蛋白表达有轻度抑制作用。免疫组化结果显示,Ad-IL-24有轻度抑制血管新生作用,ZD55治疗组有明显的抑制血管新生作用,而ZD55-IL-24治疗组血管新生几乎消失。结论:IL-24通过抑制VEGF表达和血管新生增强ZD55在体外和动物实验中的抗白血病作用。
Objective: To study the mechanism of anti-leukemia effect of interleukin-24 (IL-24) on oncolytic adenovirus (CRAd) ZD55. Methods: The infection rate of ZD55 on the leukemia cell line Mutz-1 was detected by flow cytometry. The leukemia cells were treated with ZD55, ZD55-IL-24 and non-proliferating adenovirus carrying Ad-IL-24 (Experimental group), the control group was PBS. Western blot was used to detect the effect of CRAd on the expression of vascular endothelial growth factor (VEGF) protein in leukemia cells. The expression of CD31 and VEGF in tumor-bearing tissues of Mutz-1 leukemia model was detected by immunohistochemistry. Results: The leukemic cells were infected with Z100 virus at a multiplicity of infection (MOI) of 10,100 for 48 h. The infection rates were 5.1% and 42.3%, respectively. ZD55-IL-24 significantly decreased the expression of VEGF protein, but did not significantly down-regulate VEGF after Ad-IL-24 infection. ZD55 has a slight inhibitory effect on VEGF protein expression. Immunohistochemical results showed that Ad-IL-24 had a slight inhibitory effect on angiogenesis, ZD55-treated group showed obvious inhibition of angiogenesis, while angiogenesis of ZD55-IL-24 treatment group almost disappeared. Conclusion: IL-24 enhances the anti-leukemic effect of ZD55 in vitro and in vivo by inhibiting VEGF expression and angiogenesis.