[白细胞介素-24增强条件性复制腺病毒（CRAd）ZD55抗白血病活性的机制]

[Mechanisms of enhanced antileukemia activity of conditionally replicating adenovirus (CRAd) ZD55 by interleukin-24].

作者信息

Liu Jun-qing, Yang Chun-mei, Ding Wei, Qian Wen-bin

机构信息

The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China.

出版信息

Zhejiang Da Xue Xue Bao Yi Xue Ban. 2010 May;39(3):231-5. doi: 10.3785/j.issn.1008-9292.2010.03.003.

DOI:10.3785/j.issn.1008-9292.2010.03.003

PMID:20544982

Abstract

OBJECTIVE

To investigate the mechanisms of enhanced antileukemia activity of conditionally replicating adenovirus (CRAd) by interleukin-24 (IL-24).

METHODS

The ability of CRAd ZD55 to infect leukemia cells was detected by flow cytometry. The expressions of vascular endothelial growth factor (VEGF) in leukemia cells treated with PBS, ZD55, ZD55-IL-24, and an adenovirus carrying IL-24 (Ad-IL-24) were determined by Western blot analysis. Animal xenograft tumor model was established by Mutz-1 cell line.Deparaffinized tumor sections were incubated with anti-CD31, and VEGF antibody, followed by immunohistochemistry analysis.

RESULT

The GFP-positive cells were 5.1% and 42.3% in Mutz-1 cells treated with ZD55-EGFP vector at MOI of 10 and 100 for 48h, respectively. ZD55-IL-24 treatment resulted in the marked down-regulation of VEGF protein expression and ZD55 inhibited VEGF slightly; however, there was no change observed in the cells treated with Ad-IL-24. Immunohistochemistry analysis showed that Ad-IL-24 inhibited slightly angiogenesis and ZD55 treatment resulted in significant inhibition of angiogenesis. ZD55-IL-24 treatment almost completely inhibited angiogenesis in tumor tissues.

CONCLUSION

IL-24 enhances the antileukemia activity of ZD55 by inhibiting VEGF protein expression and angiogenesis in vitro and in vivo.

摘要

目的

研究白细胞介素-24（IL-24）增强条件性复制腺病毒（CRAd）抗白血病活性的机制。

方法

采用流式细胞术检测CRAd ZD55对白血病细胞的感染能力。通过蛋白质免疫印迹分析，测定用磷酸盐缓冲液（PBS）、ZD55、ZD55-IL-24和携带IL-24的腺病毒（Ad-IL-24）处理的白血病细胞中血管内皮生长因子（VEGF）的表达。用Mutz-1细胞系建立动物异种移植肿瘤模型。将脱蜡的肿瘤切片与抗CD31和VEGF抗体孵育，随后进行免疫组织化学分析。

结果

在感染复数（MOI）为10和100的情况下，用ZD55-增强绿色荧光蛋白（EGFP）载体处理48小时后，Mutz-1细胞中绿色荧光蛋白（GFP）阳性细胞分别为5.1%和42.3%。ZD55-IL-24处理导致VEGF蛋白表达显著下调，ZD55对VEGF有轻微抑制作用；然而，用Ad-IL-24处理的细胞未观察到变化。免疫组织化学分析表明，Ad-IL-24对血管生成有轻微抑制作用，ZD55处理导致血管生成显著抑制。ZD55-IL-24处理几乎完全抑制了肿瘤组织中的血管生成。