Mechanisms of enhanced antileukemia activity of conditionally replicating adenovirus (CRAd) ZD55 by interleukin-24.
- Author:
Jun-qing LIU
1
;
Chun-mei YANG
;
Wei DING
;
Wen-bin QIAN
Author Information
- Publication Type:Journal Article
- MeSH: Adenoviridae; genetics; Animals; Apoptosis; Cell Line, Tumor; Down-Regulation; Genetic Therapy; Genetic Vectors; Humans; Interleukins; genetics; metabolism; Leukemia; metabolism; pathology; therapy; Mice; Mice, Nude; Neovascularization, Pathologic; genetics; Oncolytic Virotherapy; Platelet Endothelial Cell Adhesion Molecule-1; metabolism; Transfection; Vascular Endothelial Growth Factor A; metabolism; Xenograft Model Antitumor Assays
- From: Journal of Zhejiang University. Medical sciences 2010;39(3):231-235
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the mechanisms of enhanced antileukemia activity of conditionally replicating adenovirus (CRAd) by interleukin-24 (IL-24).
METHODSThe 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.
RESULTThe 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.
CONCLUSIONIL-24 enhances the antileukemia activity of ZD55 by inhibiting VEGF protein expression and angiogenesis in vitro and in vivo.
