[Mechanisms of enhanced antileukemia activity of conditionally replicating adenovirus (CRAd) ZD55 by interleukin-24].
To investigate the mechanisms of enhanced antileukemia activity of conditionally replicating adenovirus (CRAd) by interleukin-24 (IL-24).



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.



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.



IL-24 enhances the antileukemia activity of ZD55 by inhibiting VEGF protein expression and angiogenesis in vitro and in vivo.
Liu
Jun-qing
JQ
The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China.
Yang
Chun-mei
CM
Ding
Wei
W
Qian
Wen-bin
WB
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D015536:Down-Regulation; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D007378:Interleukins / Q000235:genetics* / Q000378:metabolism; D007938:Leukemia / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000235:genetics; D050130:Oncolytic Virotherapy; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D000099180:Interleukin-24
D007378:Interleukins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; D000099180:Interleukin-24