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

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.